Abstract
Apoptosis of hippocampal neurons is one of the mechanisms of hippocampal atrophy in posttraumatic stress disorder (PTSD), and it is also one of the important reasons of memory disorder in PTSD patients. The endoplasmic reticulum stress (ERS) mediated by activated transcription factor 6α(ATF6α)/site 1 protease (S1P)/S2P is involved in cell apoptosis, but it is not clear whether it is involved in hippocampal neuron apoptosis caused by PTSD. The PTSD rat model was constructed by the single-prolonged stress (SPS) method. The experiment was divided into two parts: (1) Control group, SPS 1d group, SPS 7d group, SPS 14d group. (2) Control group, SPS 7d group, SPS 7d+AEBSF group, control+AEBSF group. 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) is an ATF6α pathway inhibitor. The expression of ATF6α, glucose regulated protein (GRP78), S1P, S2, C/EBP homologous protein (CHOP), caspase-12 protein and mRNA in the hippocampus of PTSD rats were detected by immunohistochemistry, Western blotting and qRT-PCR. The apoptosis of hippocampal neurons was detected by TUNEL staining. In experiment 1, the protein and mRNA expression of ATF6α, GRP78 increased gradually in SPS 1d group and SPS 7d group, but decreased in SPS 14d group(P<0.01). In experiment 2, compared with the control group, the protein and mRNA expression of ATF6α, GRP78, S1P, S2P, CHOP, caspase-12 and apoptosis rate were significantly increased in SPS 7d group(P<0.01). However, the protein and mRNA expression of ATF6α, GRP78, S1P, S2P, CHOP, caspase-12 and apoptosis rate were significantly decreased after AEBSF pretreatment(P<0.01). SPS induces apoptosis of hippocampal neurons by activating ERS mediated by ATF6α, suggesting that ERS-induced apoptosis is involved in the occurrence of PTSD.
Dl-3-n-Butylphthalide Reduces Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion Through GDNF/GFRα1/Ret Signaling Preventing Hippocampal Neuron Apoptosis
