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.
Department of Environmental Health and Toxicology, School of Public Health, Dalian Medical University, Dalian 116044, China.
Zhenwei
Z
Li
Department of Environmental Health and Toxicology, School of Public Health, Dalian Medical University, Dalian 116044, China.
Qi
Q
Liu
Department of Environmental Health and Toxicology, School of Public Health, Dalian Medical University, Dalian 116044, China.
Chang
C
Liu
Department of Environmental Health and Toxicology, School of Public Health, Dalian Medical University, Dalian 116044, China.
Chunna
C
Li
Department of Environmental Health and Toxicology, School of Public Health, Dalian Medical University, Dalian 116044, China.
Yachen
Y
Li
Department of Environmental Health and Toxicology, School of Public Health, Dalian Medical University, Dalian 116044, China.
Shuangyue
S
Li
Department of Environmental Health and Toxicology, School of Public Health, Dalian Medical University, Dalian 116044, China. Electronic address: liuxh892@126.com.
Xiaohui
X
Liu
Department of Environmental Health and Toxicology, School of Public Health, Dalian Medical University, Dalian 116044, China. Electronic address: jshao@uw.edu.
Jing
J
Shao
D017738:Alkanesulfonic Acids / Q000633:toxicity*; D026962:Amino Acid Transport System ASC / Q000235:genetics; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D000071192:Autophagy-Related Protein 12 / Q000235:genetics; D000071187:Autophagy-Related Protein 5 / Q000235:genetics; D000071186:Beclin-1 / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D018920:Coculture Techniques; D005466:Fluorocarbons / Q000633:toxicity*; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D015778:Minor Histocompatibility Antigens / Q000235:genetics; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D017738:Alkanesulfonic Acids; D026962:Amino Acid Transport System ASC; D026921:Amino Acid Transport Systems, Neutral; C545865:Atg5 protein, rat; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D000071186:Beclin-1; C512829:Becn1 protein, rat; D005466:Fluorocarbons; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; D017382:Reactive Oxygen Species; C498849:Slc1a5 protein, rat; C403222:system N protein 1; C076994:perfluorooctane sulfonic acid; D053148:Caspase 3; D005974:Glutamate-Ammonia Ligase
Astrocyte-neuron co-culture; Glutamate-glutamine cycle; Neurotoxicity; Perfluorooctane sulfonate