Effects of developmental arsenite exposure on hippocampal synapses in mouse offspring

Abstract

Arsenic exposure through drinking water can impair the learning and memory ability of children in China and other countries. Synaptic plasticity plays a key role in the process of learning and memory. Alterations in the expression of presynaptic and postsynaptic proteins can be used to evaluate synaptic plasticity, and further to evaluate impairment in learning and memory ability. Thereby, the aim of this study was to explore the mechanisms underlying arsenic neurotoxicity by focusing on alterations in the hippocampal synapses of mouse offspring induced by developmental arsenite exposure. Mother mice and their offspring were exposed to 0, 25, 50 or 100 mg L arsenite via drinking water from the first day of gestation until postnatal day (PND) 35. The spatial learning and memory ability of PND 35 mice was evaluated using a Morris water maze. The levels of speciated arsenicals in the brain of PND 7, 14, 21 and 35 mice were analyzed by hydride generation coupled with atomic absorption spectrophotometry. Synaptic structure and protein expression of postsynaptic density protein-95 (PSD-95) and synaptophysin (SYP) in the hippocampus of PND 7, 14, 21 and 35 mice were examined. The findings from this study disclosed that the spatial learning ability of mice could be impaired by exposure to 25 mg L arsenite; however spatial memory ability could not be impaired until exposure to 100 mg L arsenite. The thickness of the postsynaptic density (PSD) decreased, whereas the width of the synaptic cleft widened significantly in arsenite exposure groups. Moreover, protein expression of both PSD-95 and SYP decreased significantly in arsenite exposure groups. In conclusion, the results of this study demonstrated that developmental arsenite exposure could depress the expression of synaptic proteins, subsequently cause alteration in synaptic structures, and finally contribute to arsenite-induced deficits in spatial learning and memory ability in mouse offspring.

Gas chromatography‐mass spectrometry based metabolomics profile of hippocampus and cerebellum in mice after chronic arsenic exposure

“…The PSD thickness is closely relevant to synaptic transmission and plasticity, which, therefore, is an important indicator of its function in learning and memory. In line with our study, As‐induced PSD thickness reduction was found related to hippocampal deficits, indicating neurodegeneration in CNS …”

Fasudil alleviates brain damage in rats after carbon monoxide poisoning through regulating neurite outgrowth inhibitor/oligodendrocytemyelin glycoprotein signalling pathway

“…27 Zhao and colleagues found that the thickness of the postsynaptic density (PSD) decreased in hippocampus in an animal model after exposure to Arsenic, whereas the width of the synaptic cleft widened notably, and protein expressions of both PSD-95 and synaptophysin (SYP) decreased significantly. 28 In the present study, TEM analysis also showed some morphological and structural changes of synapsis in CO group including the less number of synapses and synaptic vesicles, the little thickness of PSD and the small curvature of the synaptic interface. However, there was no statistical difference between CO group and Fasudil group, and this result was slightly different from the data of Egawa and Zhao.…”

“…Combined with the measurable electrophysiological changes, these ultrastructural alterations in hippocampus improved learning and memory, suggesting that caveolin‐1 (Cav‐1) may be an attractive molecular target to repair brain function in the context of neurodegenerative diseases . Zhao and colleagues found that the thickness of the postsynaptic density (PSD) decreased in hippocampus in an animal model after exposure to Arsenic, whereas the width of the synaptic cleft widened notably, and protein expressions of both PSD‐95 and synaptophysin (SYP) decreased significantly . In the present study, TEM analysis also showed some morphological and structural changes of synapsis in CO group including the less number of synapses and synaptic vesicles, the little thickness of PSD and the small curvature of the synaptic interface.…”

Alterations of NMDA and AMPA receptors and their signaling apparatus in the hippocampus of mouse offspring induced by developmental arsenite exposure

“…As described in our previous study (Zhao et al, 2017), no poisoning symptoms in both the mother mice and their pups were observed during experimental period. Furthermore, the body weights of the pups in all the groups increased along with the number of postnatal days.…”

“…Our previous study found that developmental arsenite exposure lead to impaired spatial learning and memory abilities in mice (Zhao et al, 2017). Since NMDARs, AMPARs, CaMKII and phosphorylated-CaMKII (p-CaM-KII) play important role in neuronal functions of cognitive and intellectual abilities, we hypothesized that developmental arsenite exposure might induce cognitive deficits with altered expression of NMDAR subunits, AMPAR subunits, CaMKII and p-CaMKII in the hippocampus of offspring mice.…”