title: Protective effects of perindopril on d-galactose and aluminum trichloride induced neurotoxicity via the apoptosis of mitochondria-mediated intrinsic pathway in the hippocampus of mice.
abstract: Perindopril, an angiotensin converting enzyme inhibitor, has been reported to improve learning and memory in a mouse or rat model of Alzheimer's disease (AD) induced by injection of beta-amyloid protein. However, the exact mechanism of perindopril on the cognitive deficits is not fully understood. Our previous data have indicated that perindopril improves learning and memory in a mouse model of AD induced by D-galactose (D-gal) and aluminum trichloride (AlCl₃) via inhibition of acetylcholinesterase activity and oxidative stress. Whether perindopril also inhibit apoptosis to prevent cognitive decline remains unknown in mice. Therefore, the present study explored the protective effects of perindopril in the hippocampus of mice further. Perindopril (0.5 mg/kg/day) was administered intragastrically for 60 days after the mice were given a D-gal (150 mg/kg/day) and AlCl₃ (10 mg/kg/day) intraperitoneally for 90 days. Then the expression of Bcl-2, Bax, Fas, FasL, caspase-3, caspase-8 and caspase-9 were analyzed by RT-PCR and western blotting in the hippocampus. Perindopril significantly decreased caspase-3 and caspase-9 activities, and elevated Bcl-2/Bax ratio in the hippocampus. However, the expression of Fas, FasL and caspase-8 did not change in the hippocampus whether treatment with d-gal and AlCl₃ or perindopril. Taken together, the above findings indicated that perindopril inhibited apoptosis in the hippocampus may be another mechanism by which perindopril improves learning and memory functions in d-gal and AlCl₃ treated mice.
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Weina
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Human Anatomy, Xi'an Medical University, Xi'an, Shaanxi 710021, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Human Anatomy, Shaanxi University of Chinese Medicine, Xi'an, Shaanxi 712046, China.
authors.forename: Lianji
authors.initials: L
authors.lastname: Chen
authors.affiliation: Center of Morphology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Bingyi
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Kaige
authors.initials: K
authors.lastname: Ma
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China. Electronic address: qianyh38@mail.xjtu.edu.cn.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Qian
mesh_terms: D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000633:toxicity; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000378:metabolism; D002712:Chlorides / Q000633:toxicity; D004195:Disease Models, Animal; D004347:Drug Interactions; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism; D005690:Galactose / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000188:drug therapy / Q000209:etiology; D020913:Perindopril / Q000494:pharmacology* / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D017607:Aluminum Compounds; D000806:Angiotensin-Converting Enzyme Inhibitors; D002712:Chlorides; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D000077410:Aluminum Chloride; D053181:Caspase 8; D005690:Galactose; D020913:Perindopril
keywords: Aluminum trichloride; Apoptosis; Hippocampus; Mouse; Perindopril; d-Galactose