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Preliminary study on toxicological mechanism of golden cuttlefish (Sepia esculenta) larvae exposed to cd

BMC Genomics volume 24, Article number: 503 (2023) Cite this article

Abstract

Background

Cadmium (Cd) flows into the ocean with industrial and agricultural pollution and significantly affects the growth and development of economic cephalopods such as Sepia esculenta, Amphioctopus fangsiao, and Loligo japonica. As of now, the reasons why Cd affects the growth and development of S. esculenta are not yet clear.

Results

In this study, transcriptome and four oxidation and toxicity indicators are used to analyze the toxicological mechanism of Cd-exposed S. esculenta larvae. Indicator results indicate that Cd induces oxidative stress and metal toxicity. Functional enrichment analysis results suggest that larval ion transport, cell adhesion, and some digestion and absorption processes are inhibited, and the cell function is damaged. Comprehensive analysis of protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to explore S. esculenta larval toxicological mechanisms, and we find that among the 20 identified key genes, 14 genes are associated with neurotoxicity. Most of them are down-regulated and enriched to the neuroactive ligand-receptor interaction signaling pathway, suggesting that larval nervous system might be destroyed, and the growth, development, and movement process are significantly affected after Cd exposure.

Conclusions

S. esculenta larvae suffered severe oxidative damage after Cd exposure, which may inhibit digestion and absorption functions, and disrupt the stability of the nervous system. Our results lay a function for understanding larval toxicological mechanisms exposed to heavy metals, promoting the development of invertebrate environmental toxicology, and providing theoretical support for S. esculenta artificial culture.

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Background

In recent years, heavy metals have been discharged into the ocean with pollutants generated by industries, agriculture, and healthcare, and have accumulated in large amounts in marine organisms, inducing growth inhibition and behavioral barriers [1,2,3,4,5]. Cadmium (Cd) is the most common heavy metal with high concentrations in the ocean [6,7,8]. It could increase reactive oxygen species (ROS) concentration of organisms in vivo to induce cell structure damage and biological dysfunction, including oxidative damage, DNA mutations, ion transport disorders, and protein destruction [9,10,11,12,13]. Meanwhile, Cd exposure can induce a large amount of Na+ loss in marine organisms and inhibit biological processes such as the storage of energy substances such as lipids and proteins [14,15,16].

Sepia esculenta is an economic cephalopod distributed along the eastern coast of China [17,18,19,20]. Compared to other marine organisms, S. esculenta larvae are relatively fragile, and adverse environments can significantly inhibit their development [21,22,23,24]. In previous studies, Cd has been found to reduce the hatchability of larvae, induce oxidative damage and toxic reaction, and promote the death of larvae [25,26,27]. The toxicological mechanism of Cd-exposed golden cuttlefish S. esculenta larvae is still unclear.

RNA-Seq is an important method for exploring biological differences at the molecular level [28,29,30]. In addition to model species, it has been applied to non-model mollusks in recent years [31, 32]. Recently, RNA-Seq was used to explore the toxicological mechanism of marine organisms exposed to heavy metals. Shi et al. found that the ATP-binding cassette transporters superfamily of Crassostrea angulate plays an important role in maintaining Cu concentration, regulating apolipoprotein transport, and clearing excess Cu [33]. Li and Wang showed that high concentration of Cd exposure will induce the disorder of DNA replication and transcription process, thus affecting the growth of oysters [34]. Zhao et al. indicated that Cd exposure could affect proteasome and oxidative physiology-related signaling pathways, thereby inducing oxidative stress in the kidney of Chlamys farreri [35]. Hence, Cd-exposed S. esculenta larval toxicological mechanisms can be explored through RNA-Seq.

In our research, we used superoxide dismutase (SOD), glutathione S-transferase (GST), metallothionein (MTs), and malondialdehyde (MDA) to assess the molecular responses of exposed S. esculenta. Meanwhile, we used functional enrichments to identify key terms and pathways. In addition, a comprehensive analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein-protein interaction (PPI) network was used to study Cd-exposed S. esculenta larval toxicological mechanisms. Our results laid a function for exploring the effects of heavy metal pollution on the biological processes of cephalopods. At the same time, the results further deepen the understanding of changes in oxidative and toxicity of mollusks after environmental stress, promoting the development of the mollusk breeding industry.

Materials and methods

Larval collection and exposure

In this study, larvae were hatched 28 days after the eggs were laid. After pre-experiment, it was confirmed that the LC50 (semilethal concentration) for 24 h under Cd exposure conditions was 64.7 ug/L. Then, we divided 200 larvae (mantle length (body size) = 6.2 ± 0.2 mm; weight = 62.8 ± 8.2 mg) into two groups, including the control group (C) and the 50 ug/L Cd-exposed group (Cd). Finally, larvae in both groups grew for 24 h in plastic barrels, respectively, and were collected at 0 h (C_0h), 4 h (C_4h and Cd_4h), and 24 h (C_24h and Cd_24h). We used liquid nitrogen to freeze the larvae quickly and collected them for preservation in a cryopreservation tube.

Assay of antioxidant enzymes and toxicity

SOD, MDA, and GST activities of S. esculenta larvae were measured using kits produced by Nanjing Jiancheng Bioengineering Institute, and MTs activity was measured using the kits produced by Shanghai Enzyme-linked Biotechnology. Their measuring methods were described by Marklund and Marklund [36], Eren [37], Satoh [38], and Penicaud, et al. [39], respectively.

RNA extraction and sequencing

We used the TRI Reagent method [40] with the manufacturer’s protocol to extract total RNA and identified the integrity using Agilent 2100 bioanalyzer [41], and the whole larva was used for RNA extraction. We selected three larvae from each group and mixed their RNA based on molar masses into a biological repeat, and repeated this process three times. We used these three replicates to construct the library [42]. Raw reads were sequenced by Illumina NovaSeq 6000 (Illumina, USA), and low-quality reads were removed. Then, HISAT2 was used to map obtained clean reads to the reference genome of our laboratory (unpublished).

DEG identification and functional enrichment analyses

In each time point, DESeq2 thresholds p-value ≤ 0.05 and fold change ≥ 1.5 was used to identify differentially expressed genes (DEGs) [43]. Then, DEGs were enriched into terms and pathways using DAVID to identify their functions [44].

Identification and validation of key and genes

Genes enriched in significant signaling pathways were used to construct a PPI network using STRING [45]. The key and hub genes were identified based on KEGG enrichment and PPI network analysis, and the accuracy of key and hub genes was verified using qRT-PCR [46]. Table S1 shows their primer sequences.

Results

Oxidative stress and metal toxicity

Figure 1 shows that the activities of SOD, MDA, GST, and MTs increase significantly after 4 h exposure. Among these, the activity of MTs increases significantly at 4 h of exposure and does not change significantly within 4 to 24 h. SOD, MDA, and GST activities exhibit a significant dose-dependent increase (p-value < 0.05) with the extension of exposure time.

Fig. 1
figure 1

Results of SOD (A), MDA (B), GST (C), and MTs (D) activities. a, b, and c stand for significant differences between exposure times

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Sequencing results and DEGs expression

An average of 43,963,462 raw reads and 43,385,588 (98.69%) clean reads are sequenced (Table S2). The Volcano plot results reveal that at 4 h exposure, 207 genes are up-regulated, and 301 genes are down-regulated. At 24 h exposure, 257 genes are up-regulated, and 161 genes are down-regulated (Fig. 2). In addition, Fig. 3 illustrates that there are 896 DEGs within 24 h of exposure, and 30 of these DEGs are expressed differently at two time points. The expression distribution of the DEGs is presented in the heatmap (Fig. 4).

Fig. 2
figure 2

Expression difference of DEGs. (A) DEGs expression distribution at 4 h exposure. Up-regulated, down-regulated, and non-regulated genes are indicated by pink, blue, and grey dots, respectively. (B) DEGs expression distribution at 24 h exposure

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Fig. 3
figure 3

DEG distributions between two time points. Different colors represent different DEGs expression distributions

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Fig. 4
figure 4

Expression clustering of DEGs. A row indicates expressions of a DEG in each group; each column represents the expression amount of all DEGs in a group

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Functional enrichment of DEGs

This study enriched 76 significant GO terms (Fig. 5). Among them, chemical synaptic transmission, cell adhesion, and other terms are important for regulating oxidative stress. KEGG enrichment analysis suggests that level-2 KEGG signaling pathways regulating oxidation and toxic reactions such as signal transduction and cell growth and death are enriched (Fig. 6). And the enrichment of signaling pathways such as cAMP signaling pathway, PI3K-Akt signaling pathway, and lysosome signaling pathway indicates that larval oxidative stress and toxicity might be significantly induced after Cd exposure.

Fig. 5
figure 5

Top 10 significant GO terms in each classification

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Fig. 6
figure 6

Top 20 level-2 KEGG signaling pathways results. The outermost circle represents the enriched level-2 KEGG pathways, and different colors stand for different classes; the second outer circle indicates the number of genes enriched into the pathway in the background gene set; the third circle represents the gene numbers enriched into the pathway in the input gene set; rich factor stands for the ratio of the number of genes in the input gene set enriched in the pathway to enriched gene numbers in the background gene set

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Table 1 Significant level-3 KEGG signaling pathways statistics
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Key and hub genes analysis

We used 48 DEGs enriched in pathways listed in Table 1 to construct the PPI network (Fig. 7). Table 2 shows relevant parameters. Among the network, three hub genes interacting with the most genes or involving in the most pathways in Table 1, including GRIA1, GRIA4, and GRIK2, are identified; and 17 key genes with higher protein interaction numbers or higher KEGG pathway participation numbers are identified at the same time (Table 3). qRT-PCR result suggests that DEGs in Table 3 are single products, and RNA-Seq results are accurate (Fig. 8).

Fig. 7
figure 7

The PPI network. The dots stand for proteins, and the connection represents the interaction between genes

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Fig. 8
figure 8

Gene expression verification (qRT-PCR). The abscissa represents Cd exposure time; the ordinate stands for fold change

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Table 2 The network parameters
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Table 3 Summary of key and hub DEGs.
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Discussion

Purpose and significance

This study aims to reveal the effect of Cd acute exposure on the molecular mechanisms of S. esculenta larvae. In previous studies, oxidative stress, immune response, and metabolic mechanisms of cephalopods exposed to Cd were studied based on multiple experiments [39, 47, 48]. For example, Cd inhibits the energy metabolism of Sepia pharaonis by inhibiting the expression of arginine kinase [47]. Cd exposure induces oxidative stress and regulates the immune response of Sepiella maindroni by regulating the expression of HSP70 [48]. We supplemented the transcriptome analysis on the basis of experimentally exploring the oxidation and toxicity mechanisms of S. esculenta larvae to further reveal the larval response to Cd at the molecular level.

Biochemical and molecular biomarkers analysis

Cd has significant effects on ROS concentration in organisms [49, 50]. When ROS concentration is stable at normal level, it involves and regulates cell processes such as proliferation and differentiation, immune signal transduction, and transcription factor expression and plays an important role in maintaining biological life activities [51, 52]. However, excessive concentration of ROS will induce DNA strand breakage, cell function and tissue structure damage, lipid peroxidation, and other oxidative damage [53, 54]. To mitigate the adverse effects caused by oxidative damage, the organism will activate the antioxidant defense system to deal with oxidative stress, which promotes the synthesis and expression of SOD and some other antioxidant substances to remove excess ROS [55, 56]. SOD is the most important antioxidant enzyme defense system to eliminate ROS. It can catalyze superoxide anion free radicals into H2O2, which is then decomposed into water by other antioxidant enzymes to resist the oxidative stress process [55, 57]. MDA is the main product of polyunsaturated fatty acid peroxidation, which is used to identify biological lipid peroxidation degree [58,59,60]. In our study, with the increase of exposure time, the activities of SOD and MDA continue to increase, suggesting that tissues and organs of S. esculenta larvae exposed to Cd are seriously damaged by oxidation, and the integrity of membrane-related biomolecules is damaged. Meanwhile, Cd exposure can induce metal toxicity. GST is a key enzyme that regulates cell detoxification, and reduces metal toxicity by regulating GSH binding to heavy metals [61, 62]. MTs can catalyze heavy metals into metal-MT complexes to reduce the content of heavy metals in cells and reduce the damage of heavy metals to proteins and tissues by seizing heavy metal ions combined with other proteins [63, 64]. Based on our results, we speculate that Cd induces significant metal toxicity, and GST and MTs reduce toxicity by combining the excess heavy metals in S. esculenta larvae. The significant changes of SOD, MDA, GST, and MTs activities show that Cd induces oxidative stress and increases the activity of antioxidant enzymes, leading to oxidative damage in S. esculenta larvae from the effects of Cd exposure.

GO functional enrichment analysis

Ion transport, cell adhesion, and other processes are significantly inhibited in Cd-exposed larvae. Multiple terms regulating ion binding and transportation such as ion transport, calcium ion binding, and ion channel activity are significantly enriched. Cd exposure affected almost all ion transport and inhibited ion binding, thereby destroying ion homeostasis [65,66,67]. And the ion disorder could significantly affect the metabolic processes of organisms [68, 69]. We preliminarily speculate that Cd might affect the ion homeostasis of larvae by inhibiting ion transport and binding, and inducing metabolic toxicity to inhibit larval growth and development. Down-regulation of DEGs enriched in cell adhesion and muscle cell cellular homeostasis terms indicates that larval cell functions might be inhibited after Cd exposure. Among them, the destruction of cell adhesion function could inhibit the immune functions of larvae and reduce their immunity [70]. And the disorder of muscle cells might induce motor dysfunction in S. esculenta larvae and inhibit their swimming ability [71]. The enrichment of oxygen binding and oxidoreductase activity terms might be the result of Cd promoting oxidative stress and inducing oxidative damage in S. esculenta larvae, which is consistent with the results of up-regulated SOD and MDA activities in larvae exposed to Cd in this study [72, 73].

KEGG functional enrichment analysis

A large number of KEGG signaling pathways were enriched after Cd exposure. The results show that S. esculenta larvae may be adversely affected in multiple aspects such as digestion and absorption and cell functions.

Dysfunction of digestion and absorption

Digestion and absorption are essential processes to maintain the life activities of organisms [74]. Disorder of this process will significantly reduce the efficiency of energy acquisition and inhibit the absorption and transport of nutrients [75, 76]. In this study, protein digestion and absorption signaling pathway and carbohydrate digestion and absorption signaling pathway were enriched, and most DEGs enriched in pathways were down-regulated. We speculate that digestion and absorption process of carbohydrates and proteins are inhibited after Cd exposure. The down-regulation of genes enriched in relevant pathways maintaining cell and extracellular matrix structure and regulating cell functions, including collagen type VI alpha 6 chain (COL6A6) and collagen type XII alpha 1 chain (COL12A1), might be the result of Cd-induced oxidative damage to cells in the digestive system [77,78,79]. This result is consistent with the increase in SOD and MDA activities in this study. In addition, the up-regulation of solute carrier family 37 member 4 (SLC37A4) indicates that S. esculenta larvae might resist oxidative damage induced by Cd by promoting glucose metabolism and energy production to promote antioxidant reaction [80, 81]. In conclusion, we preliminarily speculate that Cd exposure might inhibit larval absorption and digestion process by inducing oxidative damage to cells. The reason for the up-regulation of SLC37A4 still needs to be elucidated in follow-up studies.

Cell functions and oxidative damage

The PI3K-AKT is a core signaling pathway regulating cellular functions such as growth, proliferation, migration, and survival [82, 83]. It plays a significant role in antioxidant reactions [84]. Previous studies have shown that oxidative stress induces tissue peroxidation, inhibits cell growth and proliferation, and induces oxidative damage to cells [84, 85]. While regulating cell function, activation of PI3K-AKT signaling pathway promotes the expression of antioxidant genes and regulates apoptosis to reduce oxidative damage to cells [86, 87]. At the same time, PI3K-AKT signaling pathway acts a key part in the repair of DNA damage caused by oxidative stress and regulation of protein synthesis [88]. In this study, the activities of two antioxidant enzymes are significantly up-regulated, suggesting that Cd may induce severe oxidative stress. And PI3K-AKT signaling pathway might reduce oxidative damage of S. esculenta larval cells by regulating cell apoptosis, DNA repair, and protein synthesis.

Cd-induced neurotoxicity based on analysis of key and hub genes

The nervous system is the most important system that regulates all physiological functions of organisms [89, 90]. It can sense and respond to changes in the internal and external environment and play a leading role in maintaining biological breathing, feeding, movement, and other life processes [91, 92]. Among the 20 key and hub genes with a high number of protein interactions or KEGG pathway participation, 14 genes, including hub gene, have been identified to regulate the stability of the nervous system in previous studies, and these genes are enriched in neuroactive ligand-receptor interaction signaling pathway that regulates nervous system functions [93]. This result suggests that Cd might significantly affect larval nervous system and induce neurotoxicity. GABBR is a receptor for the key inhibitory neurotransmitter GABA in the central nervous system and regulates the inhibition of neurons [94, 95]. Meanwhile, as an important regulator of the GABAergic system, GABBR acts a crucial part in regulating the functions of the brain [96, 97]. GABBR can be divided into two subunits, GABBR1 and GABBR2, which play key roles in neurotransmitter transmission [94, 98]. The most important function of GABBR1 and GABBR2 is to regulate synaptic transmission, and their overexpression inhibits presynaptic Ca channel functions such as Ca2+ influx, thereby inhibiting synaptic transmission in the central nervous system and inducing neurotoxicity [95, 99]. It is worth noting that Tsentsevitsky and Petrov have found in previous studies that Cd exposure reversibly blocks the voltage-gated Ca2+ channels, promoting Cd absorption [100]. The significant up-regulation of GABBRs in the present study indicates that synaptic transmission function in Cd-exposed S. esculenta larvae might be inhibited, and the absorption rate of Cd may be increased, promoting the toxicity of Cd and reducing the stability of the nervous system. Glutamate receptors (GlyRs) are another protein that regulates inhibitory neurotransmission in the central nervous system [101, 102]. GLRA1 and GLRA2, subunit encoding inhibitory glycine receptors, were found in recent years to be mainly used to regulate the stability of glycinergic inhibitory synapse functions [103, 104]. In fish, these two genes regulate the transmission of inhibitory neurotransmitters and play central roles in the regulation of motor functions. And the abnormal expression of GLRA1 and GLRA2 induces motor coordination disorder and inhibits swimming, breathing, eating and other exercise processes [103,104,105]. In this research, GLRA1 and GLRA2 are up-regulated, indicating that Cd might damage larval motor nerves and inhibit various motor processes. Hub genes, including GRIA1, GRIA4, and GRIK2, are identified to further explore changes in larval neural functions after Cd exposure. AMPA receptor is a glutamate gated cation channel which has been widely concerned because of its important neural regulation function [106, 107]. As the genes encoding the AMPA receptor components GluA1 and GluA4, GRIA1 and GRIA4 play significant roles in regulating neural functions such as synaptic development and transmission [108, 109]. And their abnormal expressions could cause the disorder of synaptic functions that induce neurodevelopmental and motor dysfunction as well as impaired memory ability and behavioral phenotypes [109, 110]. As a gene encoding another glutamate ionotropic receptor KARs in the central nervous system, GRIK2 has similar functions to GRIA1 and GRIA4 such as the regulation of neurotransmitter release and synaptic plasticity and induces neurodevelopmental disorders and decreased exercise vitality when abnormally expressed [111, 112]. Three hub genes are significantly up-regulated in this study. Based on previous studies on these three hub genes, we preliminarily speculate that Cd might significantly inhibit the development of the nervous system of S. esculenta larvae and induce neurological dysfunction. In addition, the functions of the remaining neuro-related key genes, including ADRA2C, GALR1, GRIN3A, GRM2, GRM5, GRM8, and PLG, such as neuron and synaptic transmission, maintenance of nervous system homeostasis, and regulation of ion transport have also been found in previous studies [113,114,115,116,117,118,119]. In conclusion, we preliminarily speculate that the larval nervous system has significant changes after Cd exposure. Cd might inhibit the development of nervous system and induce neurotoxicity in larvae by inhibiting neuronal and synaptic transmission, hindering ion transport, and reducing motor coordination ability and significantly inhibiting larval growth and development. However, these genes have not been studied in marine mollusks, and their functions in S. esculenta are still unclear. High concentrations of Cd in coastal areas induce oxidative damage and metal toxicity, inhibit the growth and development of marine organisms, reduce larval hatching and survival rates, and seriously hinder the artificial breeding of marine organisms. Therefore, the neurotoxicity induced by Cd in S. esculenta larvae needs to be further explored in the future.

Conclusion

We use a combination of experimental index measurement and innovative transcriptome analysis to explore Cd-exposed S. esculenta larval molecular mechanisms. The results indicate that biochemical and molecular biomarkers, including SOD, MDA, GST, and MTs, show significant changes after Cd exposure, indicating that Cd might induce peroxidation in larval tissues of S. esculenta and trigger toxic reactions. The results of transcriptome analysis showed that the digestion and absorption functions of larvae were inhibited and cells might be severely damaged by oxidation. In addition, the most important point is that larval nervous system might be destroyed, and the neural development and motor coordination of larvae might be significantly inhibited. This study preliminarily reveals Cd-exposed larval toxicological mechanisms, laying a foundation for understanding the response mechanism of cephalopods to heavy metal exposure deeply, providing theoretical support for the artificial cultivation of S. esculenta, and promoting the development of cephalopod aquaculture.

Data Availability

The datasets generated and analysed during the current study are available in the NCBI repository, accession number SRR19578101, SRR19578102, SRR19578103, SRR19578104, SRR19578105, SRR19578106, SRR19578107, SRR19578113, SRR19578114, SRR20545810, SRR20545811, SRR20545812, SRR20545813, SRR20545816, SRR20545817 at the following link: ncbi.nlm.nih.gov/Traces/study/?acc = PRJNA844162&o = library_name_s%3Aa.

References

  1. Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ. Heavy Metals toxicity and the Environment[J]. Experientia Suppl. 2012;101:133–64.

    Google Scholar 

  2. Chen J, Xu Y, Han Q, Yao Y, Xing H, Teng X. Immunosuppression, oxidative stress, and glycometabolism disorder caused by cadmium in common carp (Cyprinus carpio L): application of transcriptome analysis in risk assessment of environmental contaminant cadmium[J]. J Hazard Mater. 2019;366:386–94.

    CAS  PubMed  Google Scholar 

  3. Miao Z, Miao Z, Teng X, Xu S. Melatonin alleviates lead-induced intestinal epithelial cell pyroptosis in the common carps (Cyprinus carpio) via miR-17-5p/TXNIP axis[J]. Fish and Shellfish Immunology. 2022;131:127–36.

    CAS  PubMed  Google Scholar 

  4. Cui J, Zhou Q, Yu M, Liu Y, Teng X, Gu X. 4-tert-butylphenol triggers common carp hepatocytes ferroptosis via oxidative stress, iron overload, SLC7A11/GSH/GPX4 axis, and ATF4/HSPA5/GPX4 axis[J]. Ecotoxicol Environ Saf. 2022;242:113944.

    CAS  PubMed  Google Scholar 

  5. Sun Q, Liu Y, Teng X, Luan P, Teng X, Yin X. Immunosuppression participated in complement activation-mediated inflammatory injury caused by 4-octylphenol via TLR7/IκBα/NF-κB pathway in common carp (Cyprinus carpio) gills[J]. Aquat Toxicol. 2022;249:106211.

    CAS  PubMed  Google Scholar 

  6. Ankley GT, Daston GP, Degitz SJ, Denslow ND, Hoke RA, Kennedy SW, et al. Toxicogenomics in regulatory ecotoxicology[J]. Environ Sci Technol. 2006;40(13):4055–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Deidda I, Russo R, Bonaventura R, Costa C, Zito F. Lampiasi, N. Neurotoxicity in Marine Invertebrates: an Update[J]. Biology. 2021;10(2):161.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Zhang Z, Zheng Z, Cai J, Liu Q, Yang J, Gong Y, et al. Effect of cadmium on oxidative stress and immune function of common carp (Cyprinus carpio L.) by transcriptome analysis[J]. Aquat Toxicol. 2017;192:171–7.

    CAS  PubMed  Google Scholar 

  9. Sun M, Li Y, Liu Y, Lee SC, Wang L. Transcriptome assembly and expression profiling of molecular responses to cadmium toxicity in hepatopancreas of the freshwater crab Sinopotamon henanensep[J]. Sci Rep. 2016;6:19405.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Poynton HC, Taylor NS, Hicks J, Colson K, Chan S, Clark C. Metabolomics of microliter hemolymph samples enables an improved understanding of the combined metabolic and transcriptional responses of Daphnia magna to cadmium[J]. Environ Sci Technol. 2011;45(8):3710–7.

    CAS  PubMed  Google Scholar 

  11. Waalkes MP. Cadmium carcinogenesis[J]. Mutat Res. 2003;533(1–2):107–20.

    CAS  PubMed  Google Scholar 

  12. Qin Q, Qin S, Wang L, Lei W. Immune responses and ultrastructural changes of hemocytes in freshwater crab Sinopotamon henanense exposed to elevated cadmium[J]. Aquat Toxicol, 2012, 106–7:140–146.

  13. Lei W, Wang L, Liu D, Xu T, Luo J. Histopathological and biochemical alternations of the heart induced by acute cadmium exposure in the freshwater crab Sinopotamon yangtsekiense[J]. Chemosphere. 2011;84(5):689–94.

    CAS  PubMed  Google Scholar 

  14. Liu W, Qiu H, Yan Y, Xie X. Acute Cd Toxicity, Metal Accumulation, and Ion loss in Southern Catfish (Silurus meridionalis Chen)[J]. Toxics. 2021;9(9):202.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Ginneken MV, Jonge MD, Bervoets L, Blust R. Uptake and toxicity of cd, Cu and Pb mixtures in the isopod Asellus aquaticus from waterborne exposure[J]. Sci Total Environ. 2015;537:170–9.

    PubMed  Google Scholar 

  16. Xuan R, Wu H, Li Y, Wei B, Wang L. Comparative responses of Sinopotamon henanense to acute and sub-chronic cd exposure[J]. Volume 28. Environmental Science and Pollution Research; 2021. pp. 35038–50. 26.

  17. Liu C, Zhao F, Yan J, Liu C, Liu S, Chen S. Transcriptome sequencing and De Novo Assembly of Golden Cuttlefish Sepia esculenta Hoyle[J]. Int J Mol Sci. 2016;17(10):1749.

    PubMed  PubMed Central  Google Scholar 

  18. Kanzawa N, Ogawa T, Asakura M, Okiyama K, Honda M, Tsuchiya T. Comparative expression and tissue distribution analyses of astacin-like squid metalloprotease in squid and cuttlefish[J]. Zoolog Sci. 2008;25(1):14–21.

    CAS  PubMed  Google Scholar 

  19. Effects of Low Salinity Stress on the Survival. Immune enzyme activity and gene expression of Sepia esculenta[J]. J Jiangsu Ocean Univ. 2020;29(2):6–14.

    Google Scholar 

  20. Fang Z, Yu J, Yangguang M, Han P. Microstructure of beak and cuttlebone and determination of growth increments for Sepia esculentas off Coast of East China Sea[J]. J Guangdong Ocean Univ. 2022;42(2):46–52.

    Google Scholar 

  21. Bai Q, Li J, Xu X, Zhang Z, Li W, Zhang X. Effects of social hierarchy on the behavioral phenotype and energy metabolism of Sepia esculenta in the reproductive period[J]. Acta Ecol Sin. 2020;40(15):5408–17.

    Google Scholar 

  22. Bian L, Liu C, Chen S, Zhao F, Ge J, Tan J. Transcriptome analysis of gene expression patterns during embryonic development in golden cuttlefish (Sepia esculenta)[J]. Genes Genomics. 2018;40(3):253–63.

    CAS  PubMed  Google Scholar 

  23. Fisher WS, DiNuzzo AR. Agglutination of bacteria and erythrocytes by serum from six species of marine molluscs[J]. J Invertebr Pathol. 1991;57(3):380–94.

    CAS  PubMed  Google Scholar 

  24. Rowley AF, Powell A. Invertebrate Immune Systems–Specific, quasi-specific, or nonspecific?[J]. J Immunol. 2007;179(11):7209–14.

    CAS  PubMed  Google Scholar 

  25. Liu H, Li H, Zhang X, Gong X, Han D, Zhang H, et al. Metabolomics comparison of metabolites and functional pathways in the gills of Chlamys farreri under cadmium exposure[J]. Environ Toxicol Pharmacol. 2021;86:103683.

    CAS  PubMed  Google Scholar 

  26. Li D, Wang P, Wang C, Fan X, Wang X, Hu B. Combined toxicity of organophosphate flame retardants and cadmium to Corbicula fluminea in aquatic sediments[J]. Environ Pollut. 2018;243(Pt A):645–53.

    CAS  PubMed  Google Scholar 

  27. Yap CK, Ismail A, Omar H, Tan SG. Toxicities and tolerances of cd, Cu, Pb and Zn in a primary producer (Isochrysis galbana) and in a primary consumer (Perna viridis)[J]. Environ Int. 2004;29:1097–104.

    CAS  PubMed  Google Scholar 

  28. Liu Y, Xin Z, Song J, Zhu X, Liu Q, Zhang D, et al. Transcriptome analysis reveals potential antioxidant defense mechanisms in Antheraea pernyi in response to Zinc Stress[J]. J Agric Food Chem. 2018;66(30):8132–41.

    CAS  PubMed  Google Scholar 

  29. Bao X, Wang W, Chen X, Feng Y, Xu X, Sun G, et al. Exploration of immune response mechanisms in cadmium and copper co-exposed juvenile golden cuttlefish (Sepia esculenta) based on transcriptome profiling[J]. Front Immunol. 2022;13:963931.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Li Z, Liu X, Liu J, Zhang K, Yu H, He Y, et al. Transcriptome profiling based on proteineprotein interaction networks provides a core set of genes for understanding blood immune response mechanisms against Edwardsiella tarda infection in japanese flounder (Paralichthys olivaceus)[J]. Volume 78. Developmental and Comparative Immunology; 2018. pp. 100–13.

  31. Li Z, Bao X, Liu X, Li Y, Cui M, Liu X, et al. Transcriptome profiling based on protein–protein interaction networks provides a set of core genes for understanding the immune response mechanisms of the egg-protecting behavior in Octopus ocellatus[J]. Fish and Shellfish Immunology. 2021;117:113–23.

    CAS  PubMed  Google Scholar 

  32. He S, You J, Liang X, Zhang Z, Zhang Y. Transcriptome sequencing and metabolome analysis of food habits domestication from live prey fish to artificial diets in mandarin fish (Siniperca chuatsi)[J]. BCM Genomics. 2021;22(1):129.

    CAS  Google Scholar 

  33. Shi B, Huang Z, Xiang X, Huang M, Wang W, Ke C. Transcriptome analysis of the key role of GAT2 gene in the hyper-accumulation of copper in the oyster Crassostrea angulate [J]. Sci Rep. 2015;5:17751.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Li Y, Wang W. Integrated transcriptomics and proteomics revealed the distinct toxicological effects of multi-metal contamination on oysters [J]. Environ Pollut. 2021;284:117533.

    CAS  PubMed  Google Scholar 

  35. Zhao Y, Kang X, Shang D, Ning J, Ding H, Zhai Y, et al. Hyperaccumulation of cadmium by scallop Chlamys farreri revealed by comparative transcriptome analysis [J]. Biometals. 2020;33(6):397–413.

    CAS  PubMed  Google Scholar 

  36. Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase[J]. Eur J Biochem. 1974;47(3):469–74.

    CAS  PubMed  Google Scholar 

  37. Sinha AK. Colorimetric assay of catalase[J]. Anal Biochem. 1972;47(2):389–94.

    CAS  PubMed  Google Scholar 

  38. Eren SH, Korkmaz I, Guven FMK, Tekin YK, Ozdemir L. Serum paraoxonase, arylesterase, and Glutathione-S-Transferase activities and oxidative stress levels in patients with mushroom Poisoning[J]. Clinics. 2018;73:e16550.

    PubMed  Google Scholar 

  39. Penicaud V, Lacoue-Labarthe T, Bustamante P. Metal bioaccumulation and detoxification processes in cephalopods: a review[J]. Environ Res. 2017;155:123–33.

    CAS  PubMed  Google Scholar 

  40. Rio DC, Ares M, Hannon GJ, Nilsen TW. Purification of RNA Using TRIzol (TRI Reagent)[J]. Cold Spring Harbor Protocols, 2010, 2010(6):5439.

  41. Sodowich BI, Fadl I, Burns C. Method validation of in vitro RNA transcript analysis on the Agilent 2100 Bioanalyzer[J]. Electrophoresis. 2007;28(14):2368–78.

    CAS  PubMed  Google Scholar 

  42. Parkhomchuk D, Borodina T, Amstislavskiy V, Banaru M, Hallen L, Krobitsch S, et al. Transcriptome analysis by strand-specific sequencing of complementary DNA[J]. Nucleic Acids Res. 2009;37(18):e123.

    PubMed  PubMed Central  Google Scholar 

  43. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2[J]. Genome Biol. 2014;15(12):550.

    PubMed  PubMed Central  Google Scholar 

  44. Jiao X, Sherman BT, Huang D, Stephens R, Baseler MW, Lane HC, et al. DAVID-WS: a stateful web service to facilitate gene/protein list analysis[J]. Bioinformatics. 2012;28(13):1805–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, et al. STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets[J]. Nucleic Acids Res. 2019;47(D1):D607–13.

    CAS  PubMed  Google Scholar 

  46. Liu X, Li Z, Wu W, Liu Y, Liu J, He Y, et al. Sequencing-based network analysis provides a core set of gene resource for understanding kidney immune response against Edwardsiella tarda infection in japanese flounder[J]. Fish and Shellfish Immunology. 2017;67:643–54.

    CAS  PubMed  Google Scholar 

  47. Si Y, Lee J, Zhao F, Yin S, Park YD, Qian G, et al. Effects of cadmium on the cuttlefish Sepia pharaonis’ arginine kinase: unfolding kinetics integrated with computational simulations[J]. J Biomol Struct Dynamics. 2016;34(8):1763–77.

    CAS  Google Scholar 

  48. Liu H, He J, Chi C, Lv Z. Identification and analysis of HSP70 from Sepiella maindroni under stress of Vibrio harveyi and Cd2+[J]. Gene. 2015;572(1):146–52.

    CAS  PubMed  Google Scholar 

  49. Kim H, Kim JS, Kim PJ, Won EJ, Lee YM. Response of antioxidant enzymes to cd and pb exposure in water flea Daphnia magna: Differential metal and age - specific patterns [J]. Volume 209. Comparative Biochemistry and Physiology C-Toxicology and Pharmacology; 2018. pp. 28–36.

  50. Yan B, Liu X, Zhao X, Tian S. Single and joint oxidative stress of cadmium and phenanthrene on the Bivalve Anadara subcrenata [J]. J Environ Sci Health Part A. 2020;55(4):448–56.

    CAS  Google Scholar 

  51. Lambeth JD, NOX ENZYMES AND, THE BIOLOGY OF REACTIVE OXYGEN[J]. Nat Rev Immunol. 2004;4(3):181–9.

    CAS  PubMed  Google Scholar 

  52. Sanchez JA, Mesquita D, Ingaramo MC, Ariel F, Milán M, Dekanty A. Eiger/TNFα-mediated Dilp8 and ROS production coordinate intra-organ growth in Drosophila [J]. PLoS Genet. 2019;15(8):e1008133.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Dilberger B, Baumanns S, Schmitt F, Schmiedl T, Hardt M, Wenzel U et al. Mitochondrial Oxidative Stress Impairs Energy Metabolism and Reduces Stress Resistance and Longevity of C. elegans[J]. Oxidative Medicine and Cellular Longevity, 2019, 2019:6840540.

  54. Ruiz-Torres V, Rodríguez-Pérez C, Herranz-López M, Martín-García B, Gómez-Caravaca AM, Arráez-Román D, et al. Marine Invertebrate extracts induce Colon cancer cell death via ROS-Mediated DNA oxidative damage and mitochondrial Impairment[J]. Biomolecules. 2019;9(12):771.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Lu X, Wang C, Liu B. The role of Cu/Zn-SOD and Mn-SOD in the immune response to oxidative stress and pathogen challenge in the clam Meretrix meretrix[J]. Fish and Shellfish Immunology. 2015;42(1):58–65.

    CAS  PubMed  Google Scholar 

  56. Yang J, Dong S, Jiang Q, Si Q, Liu X, Yang J. Characterization and expression of cytoplasmic copper/zinc superoxide dismutase (CuZn SOD) gene under temperature and hydrogen peroxide (H2O2) in rotifer Brachionus calyciflorus[J]. Gene. 2013;518(2):388–96.

    CAS  PubMed  Google Scholar 

  57. Batinic-Haberle I, Tovmasyan A, Roberts ER, Vujaskovic Z, Leong KW, Spasojevic I. SOD therapeutics: latest insights into their structure-activity relationships and impact on the cellular redox-based signaling pathways[J]. Antioxid Redox Signal. 2014;20(15):2372–415.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Li Y, Chai X, Wu H, Jing W, Wang L. The response of metallothionein and malondialdehyde after exclusive and combined Cd/Zn exposure in the crab Sinopotamon henanense[J]. PLoS ONE. 2013;8(11):e80475.

    PubMed  PubMed Central  Google Scholar 

  59. Xuan R, Wu H, Li Y, Wei B, Wang L. Comparative responses of Sinopotamon henanense to acute and sub-chronic cd exposure[J]. Environ Sci Pollut Res. 2021;28(26):35038–50.

    CAS  Google Scholar 

  60. Tsikas D. Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: Analytical and biological challenges[J]. Anal Biochem. 2017;524:13–30.

    CAS  PubMed  Google Scholar 

  61. Nicosia A, Celi M, Vazzana M, Damiano MA, Parrinello N, D’Agostino F, Part C et al. 2014, 166:14–23.

  62. Wang L, Peng Y, Nie X, Pan B, Ku P, Bao S, Part C. 2016, 179:49–56.

  63. Wang Y, Tian X, Zhu C, Yu X, Miao Y, Qiao H. Genetics of metallothioneins in Drosophilamelanogaster[J]. Chemosphere. 2022;288(2):132562.

    CAS  Google Scholar 

  64. Calvo J, Jung H, Meloni G. Copper metallothioneins[J]. IUBMB Life. 2017;69(4):236–45.

    CAS  PubMed  Google Scholar 

  65. Castaldo G, Flipkens G, Pillet M, Town RM, Bervoets L, Blust R, et al. Antagonistic bioaccumulation of waterborne cu(II) and cd(II) in common carp (Cyprinus carpio) and effects on ion-homeostasis and defensive mechanisms[J]. Aquat Toxicol. 2020;226:105561.

    CAS  PubMed  Google Scholar 

  66. Poteat MD, Buchwalter DB. Calcium uptake in aquatic insects: influences of phylogeny and metals (cd and zn). J Exp Biol. 2014;217(7):1180–6.

    CAS  PubMed  Google Scholar 

  67. Issartel J, Boulo V, Wallon S, Geffard O, Charmantier G. Cellular and molecular osmoregulatory responses to cadmium exposure in Gammarus fossarum (Crustacea, Amphipoda)[J]. Chemosphere. 2010;81(6):701–10.

    CAS  PubMed  Google Scholar 

  68. Skelly PJ, Da’dara AA, Li X, Castro-Borges W, Wilson RA. Schistosome feeding and regurgitation[J]. PLoS Pathog. 2014;10(8):e1004246.

    PubMed  PubMed Central  Google Scholar 

  69. Nelson N. Metal ion transports and homeostasis[J]. EMBO J. 1999;18(16):4361–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Ratheesh A, Belyaeva V, Siekhaus DE. Drosophila immune cell migration and adhesion during embryonic development and larval immune responses[J]. Curr Opin Cell Biol. 2015;36:71–9.

    CAS  PubMed  Google Scholar 

  71. Lacalli TC. New perspectives on the evolution of protochordate sensory and locomotory systems, and the origin of brains and heads[J]. Philosophical Trans Royal Soc Lond Ser B. 2001;356(1414):1565–72.

    CAS  Google Scholar 

  72. Betteridge DJ. What is oxidative stress?[J]. Metabolism-clinical and Experimental. 2000;49(2):3–8.

    CAS  PubMed  Google Scholar 

  73. Zhang Y, Chen R, Liu X, Zhu M, Li Z, Wang A, et al. Oxidative stress, apoptosis, and transcriptional responses in Acropora microphthalma under simulated diving activities[J]. Mar Pollut Bull. 2022;183:114084.

    CAS  PubMed  Google Scholar 

  74. Miguel-Aliaga I, Jasper H, Lemaitre B. Anatomy and physiology of the Digestive Tract of Drosophila melanogaster[J]. Genetics. 2018;210(2):357–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Sun J, Liu X, Wang Z, Yin F, Liu H, Nakamura Y, et al. Gastrointestinal digestion and absorption characterization in vitro of zinc-chelating hydrolysate from scallop adductor (Patinopecten yessoensis)[J]. J Sci Food Agric. 2022;102(8):3277–86.

    CAS  PubMed  Google Scholar 

  76. Hartenstein V, Martinez P. Structure, development and evolution of the digestive system[J]. Cell Tissue Res. 2019;377(3):289–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Qiao H, Feng Y, Tang H. COL6A6 inhibits the proliferation and metastasis of non-small cell lung cancer through the JAK signalling pathway[J]. Translational Cancer Research. 2021;10(10):4514–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Shaye DD, Greenwald I. OrthoList: a compendium of C. elegans genes with human orthologs[J]. PLoS ONE. 2011;6(5):e20085.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Wu Y, Xu Y. Integrated bioinformatics analysis of expression and gene regulation network of COL12A1 in colorectal cancer[J]. Cancer Med. 2020;9(13):4743–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Gaudet P, Livstone MS, Lewis SE, Thomas PD. Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium[J]. Brief Bioinform. 2011;12(5):449–62.

    PubMed  PubMed Central  Google Scholar 

  81. Chou JY, Mansfield BC. The SLC37 family of Sugar-Phosphate/Phosphate Exchangers[J]. Curr Top Membr. 2014;73:357–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Esteban-Collado J, Corominas M, Serras F. Nutrition and PI3K/Akt signaling are required for p38-dependent regeneration[J]. Development. 2021;148(8):197087.

    Google Scholar 

  83. Abou-El-Naga IF, Review. Schistosoma mansoni phosphatidylinositol 3 kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway[J]. Comp Biochem Physiol B. 2021;256:110632.

    CAS  PubMed  Google Scholar 

  84. Wang T, Cheng J, Wang S, Wang X, Jiang H, Yang Y, et al. α-Lipoic acid attenuates oxidative stress and neurotoxicity via the ERK/Akt-dependent pathway in the mutant hSOD1 related Drosophila model and the NSC34 cell line of amyotrophic lateral sclerosis[J]. Brain Res Bull. 2018;140:299–310.

    CAS  PubMed  Google Scholar 

  85. Klaunig JE, Wang Z, Pu X, Zhou S. Oxidative stress and oxidative damage in chemical carcinogenesis[J]. Toxicol Appl Pharmcol. 2011;254(2):86–99.

    CAS  Google Scholar 

  86. Bartholome A, Kampkötter A, Tanner S, Sies H, Klotz LO. Epigallocatechin gallate-induced modulation of FoxO signaling in mammalian cells and C. elegans: FoxO stimulation is masked via PI3K/Akt activation by hydrogen peroxide formed in cell culture[J]. Arch Biochem Biophys. 2010;501(1):58–64.

    CAS  PubMed  Google Scholar 

  87. Yuan S, Huang C, Ji X, Ma M. Main Signaling Pathways and Detection methods of oxidative stress caused by environmental Pollutants[J]. Asian J Ecotoxicol. 2017;12(1):25–37.

    Google Scholar 

  88. Xie C, Kong J, Zhao C, Xiao Y, Peng T, Liu Y, et al. Molecular characterization and function of a PTEN gene from Litopenaeus vannamei after Vibrio alginolyticus challenge[J]. Dev Comp Immunol. 2016;59:77–88.

    CAS  PubMed  Google Scholar 

  89. Watson AH. Presynaptic modulation of sensory afferents in the invertebrate and vertebrate nervous system[J]. Comp Biochem Physiol A. 1992;103(2):227–39.

    CAS  Google Scholar 

  90. Farley A, Johnstone C, Hendry C, McLafferty E. Nervous system: part 1[J]. Nurs Standard. 2014;28(31):46–51.

    Google Scholar 

  91. Hendry C, Farley A, McLafferty E, Johnstone C. Nervous system: part 2[J]. Nurs Standard. 2014;28(32):45–9.

    Google Scholar 

  92. Farley A, McLafferty E, Johnstone C, Hendry C. Nervous system: part 3[J]. Nurs Standard. 2014;28(33):46–50.

    Google Scholar 

  93. Kong Y, Liang X, Liu L, Zhang D, Wan C, Gan Z, et al. High throughput sequencing identifies MicroRNAs mediating α-Synuclein toxicity by targeting neuroactive-ligand receptor Interaction Pathway in Early Stage of Drosophila Parkinson’s Disease Model[J]. PLoS ONE. 2015;10(9):e0137432.

    PubMed  PubMed Central  Google Scholar 

  94. Schultheis C, Brauner M, Liewald JF, Gottschalk A. Optogenetic analysis of GABAB receptor signaling in Caenorhabditis elegans motor neurons[J]. J Neurophysiol. 2011;106(2):817–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Dittman JS, Kaplan JM. Behavioral impact of neurotransmitter-activated G-protein-coupled receptors: muscarinic and GABAB receptors regulate Caenorhabditis elegans locomotion[J]. J Neurosci. 2008;28(28):7104–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Dhillon I, Momin A, Chin-Sang I. GABA Receptor mutant gbb-1 accelerates morphological aging of GABA neurons in Caenorhabditis elegans[J]. microPublication Biology, 2018, 2018:10.

  97. Zhao Y, Peng S, Jiang H, Du J, Yu S, Zhao M. Variants in GABBR1 gene are Associated with Methamphetamine Dependence and two years’ relapse after Drug Rehabilitation[J]. J Neuroimmune Pharmacol. 2018;13(4):523–31.

    PubMed  Google Scholar 

  98. Sorkaç A, DiIorio MA, O’Hern PJ, Baskoylu SN, Graham HK, Hart AC. LIN-12/Notch regulates GABA Signaling at the Caenorhabditis elegans Neuromuscular Junction[J]. G3-Genes genomes Genetics, 2018, 8(8):2825–32.

  99. Chalifoux JR, Carter AG. GABAB receptors modulate NMDA receptor calcium signals in dendritic spines[J]. Neuron. 2010;66(1):101–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Tsentsevitsky AN, Petrov AM. Synaptic mechanisms of cadmium neurotoxicity[J]. Neural Regeneration Research. 2021;16(9):1762–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Moroz LL, Nikitin MA, Poličar PG, Kohn AB, Romanova DY. Evolution of glutamatergic signaling and synapses[J]. Neuropharmacology. 2021;199:108740.

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Samarut E, Chalopin D, Riché R, Allard M, Liao M, Drapeau P. Individual knock out of glycine receptor alpha subunits identifies a specific requirement of glra1 for motor function in zebrafish[J]. PLoS ONE. 2019;14(5):e0216159.

    PubMed  PubMed Central  Google Scholar 

  103. Frazier SJ, Cohen BN, Lester HA. An engineered glutamate-gated chloride (GluCl) channel for sensitive, consistent neuronal silencing by ivermectin[J]. J Biol Chem. 2013;288(29):21029–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Leacock S, Syed P, James VM, Bode A, Kawakami K, Keramidas A, et al. Structure/Function studies of the α4 subunit reveal evolutionary loss of a GlyR subtype involved in startle and escape Responses[J]. Front Mol Neurosci. 2018;11:23.

    PubMed  PubMed Central  Google Scholar 

  105. Zhan F, Wang S, Cao L. Advances in hyperekplexia and other startle syndromes[J]. Neurol Sci. 2021;42(10):4095–107.

    PubMed  Google Scholar 

  106. Hoerndli FJ, Brockie PJ, Wang R, Mellem JE, Kallarackal A, Doser RL, et al. MAPK signaling and a mobile scaffold complex regulate AMPA receptor transport to modulate synaptic strength[J]. Cell Rep. 2022;38(13):110577.

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Brown ER, Piscopo S, Chun JT, Francone M, Mirabile I, D’Aniello A. Modulation of an AMPA-like glutamate receptor (SqGluR) gating by L- and D-aspartic acids[J]. Amino Acids. 2007;32(1):53–7.

    CAS  PubMed  Google Scholar 

  108. Lima PA, Nardi G, Brown ER. AMPA/kainate and NMDA-like glutamate receptors at the chromatophore neuromuscular junction of the squid: role in synaptic transmission and skin patterning[J]. Eur J Neurosci. 2003;17(3):507–16.

    PubMed  Google Scholar 

  109. Morrison GE, Kooy D. A mutation in the AMPA-type glutamate receptor, glr-1, blocks olfactory associative and nonassociative learning in Caenorhabditis elegans[J]. Behav Neurosci. 2001;115(3):640–9.

    CAS  PubMed  Google Scholar 

  110. Geisheker MR, Heymann G, Wang T, Coe BP, Turner TN, Stessman HAF, et al. Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains[J]. Nat Neurosci. 2017;20(8):1043–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Hao H, Zuo Y, Fang J, Sun A, Aioub AAA, Hu Z. Transcriptome analysis of Aedes albopictus (Diptera: Culicidae) Larvae exposed with a sublethal dose of Haedoxan A[J]. J Med Entomol. 2021;58(6):2284–91.

    CAS  PubMed  Google Scholar 

  112. Guzmán YF, Ramsey K, Stolz JR, Craig DW, Huentelman MJ, Narayanan V, et al. A gain-of-function mutation in the GRIK2 gene causes neurodevelopmental deficits[J]. Neurol Genet. 2017;3(1):e129.

    PubMed  PubMed Central  Google Scholar 

  113. Brocos-Mosquera I, Miranda-Azpiazu P, Muguruza C, Corzo-Monje V, Morentin B, Meana JJ, et al. Differential brain ADRA2A and ADRA2C gene expression and epigenetic regulation in schizophrenia. Effect of antipsychotic drug treatment[J]. Translational Psychiatry. 2021;11(1):643.

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Rizzo MJ, Evans JP, Burt M, Saunders CJ, Johnson EC. Unexpected role of a conserved domain in the first extracellular loop in G protein-coupled receptor trafficking[J]. Biochem Biophys Res Commun. 2018;503(3):1919–26.

    CAS  PubMed  Google Scholar 

  115. Murillo A, Navarro AI, Puelles E, Zhang Y, Petros TJ, Pérez-Otaño I. Temporal Dynamics and neuronal specificity of Grin3a expression in the mouse Forebrain[J]. Cereb Cortex. 2021;31(4):1914–26.

    PubMed  Google Scholar 

  116. Jeong H, Paik YK. MGL-1 on AIY neurons translates starvation to reproductive plasticity via neuropeptide signaling in Caenorhabditis elegans[J]. Dev Biol. 2017;430(1):80–9.

    CAS  PubMed  Google Scholar 

  117. Xu J, Marshall JJ, Kraniotis S, Nomura T, Zhu Y, Contractor A. Genetic disruption of Grm5 causes complex alterations in motor activity, anxiety and social behaviors[J]. Behav Brain Res. 2021;411:113378.

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Bauer LO, Covault JM. GRM8 genotype is associated with externalizing disorders and greater inter-trial variability in brain activation during a response inhibition task[J]. Clin Neurophysiol. 2020;131(6):1180–6.

    PubMed  PubMed Central  Google Scholar 

  119. Mapanao R, Rangabpai T, Lee YR, Kuo H, Cheng W. The effect of banana blossom on growth performance, immune response, disease resistance, and anti-hypothermal stress of Macrobrachium rosenbergii[J]. Fish and Shellfish Immunology. 2022;124:82–91.

    CAS  PubMed  Google Scholar 

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Funding

This research was supported by the earmarked fund for CARS-49, and the Natural Science Foundation of Shandong Province (No. ZR2019BC052).

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Authors and Affiliations

  1. College of Life Sciences, Yantai University, Yantai, 264005, China

    Xiumei Liu

  2. School of Agriculture, Ludong University, Yantai, 264025, China

    Xiaokai Bao, Jianmin Yang & Zan Li

  3. Fishery Technology Service Center of Lanshan District, Rizhao, 276800, China

    Xibo Zhu

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Contributions

XL was a major contributor in writing the manuscript. XL, XB and ZL performed the experiment and analyzed the data. XZ and ZL were the major contributors in reviewing the manuscript. JY and ZL were the major contributors in funding acquisition. All authors read and approved the final manuscript.

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Correspondence to Xibo Zhu or Zan Li.

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The experimental protocols were reviewed and approved by the Animal Care and Ethics Committee of the Ludong University (protocol number: LDU-IRB20210308NXY). The present study was reported according to the recommendation of ARRIVE guidelines for animal research. The method and process were carried out in accordance with relevant guidelines and regulations.

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Liu, X., Bao, X., Yang, J. et al. Preliminary study on toxicological mechanism of golden cuttlefish (Sepia esculenta) larvae exposed to cd. BMC Genomics 24, 503 (2023). https://doi.org/10.1186/s12864-023-09630-9

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BMC Genomics

ISSN: 1471-2164

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