Evaluation of PFOS-mediated neurotoxicity in rat primary neurons and astrocytes cultured separately or in co-culture.
Perfluorooctane sulfonate (PFOS) is a potential neurotoxicant reported by epidemiological investigations and experimental studies, while the underlying mechanisms are still unclear. Astrocytes not only support for the construction of neurons, but also conduct neuronal functions through glutamate-glutamine cycle in astrocyte-neuron crosstalk. In the present study, the effect of PFOS exposure on rat primary hippocampal neurons or cortex astrocytes was evaluated. Then the role of the astrocytes in PFOS-induced toxic effect on neurons was explored with astrocyte-neuron co-culture system. Exposure of rat primary hippocampal neurons to PFOS has led to oxidation-antioxidation imbalance, increased apoptosis and abnormal autophagy. The adverse effect of PFOS on rat primary cortex astrocytes manifested in the form of altered extracellular glutamate and glutamine concentrations, decreased glutamine synthase activity, as well as decreased gene expression of glutamine synthase, glutamate transporters and glutamine transporters in the glutamate-glutamine cycle. Especially, the alleviation of PFOS-inhibited neurite outgrowth in neurons could be observed in astrocyte-neuron co-culture system, though the ability of astrocytes in fostering neurite outgrowth was affected by PFOS. These results indicated that both astrocytes and neurons might be the targets of PFOS-induced neurotoxicity, and astrocytes could protect against PFOS-inhibited neurite outgrowth in primary cultured neurons. Our research might render some information in explaining the mechanisms of PFOS-induced neurotoxicity.
['Li|Zhenwei|Z|', 'Liu|Qi|Q|', 'Liu|Chang|C|', 'Li|Chunna|C|', 'Li|Yachen|Y|', 'Li|Shuangyue|S|', 'Liu|Xiaohui|X|', 'Shao|Jing|J|']
D017738:Alkanesulfonic Acids D026962:Amino Acid Transport System ASC D026921:Amino Acid Transport Systems, Neutral D000818:Animals D000831:Animals, Newborn D017209:Apoptosis D001253:Astrocytes D000071192:Autophagy-Related Protein 12 D000071187:Autophagy-Related Protein 5 D000071186:Beclin-1 D053148:Caspase 3 D002470:Cell Survival D002478:Cells, Cultured D002540:Cerebral Cortex D018920:Coculture Techniques D005466:Fluorocarbons D005974:Glutamate-Ammonia Ligase D006624:Hippocampus D008297:Male D008869:Microtubule-Associated Proteins D015778:Minor Histocompatibility Antigens D009474:Neurons D017208:Rats, Wistar D017382:Reactive Oxygen Species
Neurotoxicity Perfluorooctane sulfonate Glutamate-glutamine cycle Astrocyte-neuron co-culture