Chronic embryonic arsenic and mercury exposure-induced developmental neurotoxicity, neurobehavioral dysfunction and metabolic alteration in zebrafish (Daniorerio F.Hamilton, 1822)
Arsenic and mercury are ubiquitous in the environment. Exposure to these toxicants at low concentrations is unremarkable in developing organism. Nevertheless, their long-term adverse effects are underestimated and their association with cognitive deficits, one of the major criteria for neurodeve...
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| Main Author: | |
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| Format: | Thesis |
| Language: | English English |
| Published: |
2022
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/112029/1/FS%202022%2063%20-%20IR%28UPM%29.pdf http://psasir.upm.edu.my/id/eprint/112029/ |
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| Summary: | Arsenic and mercury are ubiquitous in the environment. Exposure to these
toxicants at low concentrations is unremarkable in developing organism.
Nevertheless, their long-term adverse effects are underestimated and their
association with cognitive deficits, one of the major criteria for
neurodevelopmental disorders (NDD) remains a challenge to understand. This
study investigated the long-term effects of embryonic exposure to arsenic and
mercury at low environmentally relevant concentrations on developmental
neurotoxicity, neurobehavioral dysfunction, and metabolic alteration in the
developing zebrafish. Chronic embryonic exposure to arsenic trioxide (As2O3)
or mercury chloride (HgCl2) from gastrulation to hatching resulted in
developmental neurotoxicity, neurobehavioral dysfunction, and metabolic
alteration in the treated larvae. Embryonic exposure to As2O3 or HgCl2 induced
hypo-/hyperlocomotion, affecting common metabolic pathways, particularly
arachidonic and linoleic acid metabolism. Downregulation of docosahexaenoic
acid (DHA) metabolites results in reduction of eyes, lens, and retinas diameter,
and impaired microridges for both As2O3 and HgCl2 exposure. Long-term
impairment of learning by As2O3 exposure was evident in a lack of directional
and color preference responses in adult zebrafish correspond with depletion of
both arachidonic acid and DHA metabolites. Lower survivability in HgCl2
exposed larvae compared to As2O3 could be related to the inflammatory
response and abnormal inflation of swim bladder. Transcriptional evaluation of
adsl, shank3a, tsc1b and nrxn revealed association between embryonic
exposure to As2O3 and HgCl2 with autism spectrum disorder (ASD). In this
study, zebrafish was successfully developed as an animal model for evaluation
of the long-term neurotoxicity effects of toxicants by integrating toxicity,
behavior, metabolomics, and gene expression to understand the underlying
behavioural disorders associated with NDDs. Thus, highlighting the risk of exposure to low concentrations of As/Hg for long-term duration. Considering
the ubiquity of As2O3 and HgCl2 in the environment, this study proves that
arsenic and mercury as one of the risk factors for NDDs, especially ASD in the
human population |
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