title: C/EBP homologous protein (CHOP) deficiency aggravates hippocampal cell apoptosis and impairs memory performance.
abstract: Neurodegenerative disorders are growing burdens in modern societies because of increased life expectancy. Most neurodegenerative disorders commonly possess a similar neuropathological feature--the accumulation of abnormal protein aggregates or inclusions (misfolded proteins) in the brain. One of the main functions of endoplasmic reticulum (ER) is to initiate proper protein folding to facilitate protein secretion through the induction of unfolded protein response (UPR). C/EBP homologous protein (CHOP) induction has been demonstrated to be a signaling event underlying ER stress-induced cell apoptosis. In this study, we explored the role of CHOP in the hippocampal cell apoptosis and memory performance injury under an induced ER stress condition. Adult male wild type (C57BL/6J) and CHOP knockout (CHOP-/-) mice were intracerebroventricularly injected with tunicamycin. Tunicamycin can induce ER stress and cell apoptosis in mouse hippocampus. Compared with wild type mice, CHOP-/- mice showed an enhanced hippocampal cell apoptosis, worse performance in memory-related behavioral tests, and attenuated IRE-1 expression under tunicamycin treatment. The aggravated cell apoptosis and worse memory performance in CHOP-/- mice might be due to the deficiency of CHOP protein resulted in the impaired adaptive/pathological transcriptional response, the decreased IRE-1 and XBP-1 expressions, and the increased JNK phosphorylation to cope with ER stress. Taken together, these results suggest that CHOP may play a protective role in the hippocampal cell apoptosis and impairment of memory performance.
authors: Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan. cmchen10@ms27.hinet.net
authors: Chang-Mu
authors: CM
authors: Chen
authors: Cheng-Tien
authors: CT
authors: Wu
authors: Chih-Kang
authors: CK
authors: Chiang
authors: Bor-Wu
authors: BW
authors: Liao
authors: Shing-Hwa
authors: SH
authors: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001522:Behavior, Animal / Q000187:drug effects; D053454:Caspase 12 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D051742:Transcription Factor CHOP / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: C497250:Ddit3 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D014415:Tunicamycin; D051742:Transcription Factor CHOP; D053454:Caspase 12; D053453:Caspase 9