PERK signalling pathway mediates single prolonged stress-induced dysfunction of medial prefrontal cortex neurons

Springer Science and Business Media LLC - Tập 22 - Trang 753-768 - 2017
Lili Wen1, Bing Xiao1, Yuxiu Shi1, Fang Han1
1PTSD Lab, Department of Histo-Embryology, Basic Medical Sciences College, China Medical University, Shenyang, China

Tóm tắt

Post-traumatic stress disorder (PTSD) is characterized with abnormal learning and memory. Impairments in learning and memory are closely associated with apoptosis in the medial prefrontal cortex (mPFC). We previously examined the endoplasmic reticulum (ER) stress was involved in the apoptosis in the mPFC of PTSD. The PERK pathway plays the important role in the ER stress-induced apoptosis. The aim of the present study was to explore the role of PERK pathway in neuronal apoptosis in the mPFC of rat models of PTSD. We used the single prolonged stress (SPS) to mimic PTSD in rats and studied the effects of the PERK pathway in mPFC. Learning and memory behavior were examined by Morris water maze and novel object recognition tests. Apoptosis in mPFC was detected by TUNEL staining. Our results showed decreased learning memory and increased apoptosis of mPFC neurons in rats exposed to SPS. SPS exposure upregulate mRNA expressions of PERK, p-PERK, eIF2α, p-eIF2α, nuclear ATF4 and C/EBP-homologous protein (CHOP) in mPFC neurons, but the protein levels of these molecules showed difference in magnitude and time course. GSK2606414 (an antagonist of PERK) treatment successfully reversed the above changes. These results suggested that the PERK pathway mediated SPS-induced neural apoptosis in the mPFC. These findings will be helpful in understanding mPFC-related pathogenesis of PTSD.

Tài liệu tham khảo

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