title: Chronic administration of isocarbophos induces vascular cognitive impairment in rats.
abstract: Vascular dementia, being the most severe form of vascular cognitive impairment (VCI), is caused by cerebrovascular disease. Whether organophosphorus causes VCI remains unknown. Isocarbophos (0.5 mg/kg per 2 days) was intragastrically administrated to rats for 16 weeks. The structure and function of cerebral arteries were assayed. The learning and memory were evaluated by serial tests of step-down, step-through and morris water maze. Long-term administration of isocarbophos reduced the hippocampal acetylcholinesterase (AChE) activity and acetylcholine (ACh) content but did not alter the plasma AChE activity, and significantly damaged the functions of learning and memory. Moreover, isocarbophos remarkably induced endothelial dysfunction in the middle cerebral artery and the expressions of ICAM-1 and VCAM-1 in the posterior cerebral artery. Morphological analysis by light microscopy and electron microscopy indicated disruptions of the hippocampus and vascular wall in the cerebral arteries from isocarbophos-treated rats. Treatment of isocarbophos injured primary neuronal and astroglial cells isolated from rats. Correlation analysis demonstrated that there was a high correlation between vascular function of cerebral artery and hippocampal AChE activity or ACh content in rats. In conclusion, chronic administration of isocarbophos induces impairments of memory and learning, which is possibly related to cerebral vascular dysfunction.
authors.affiliation: Department of Pharmacology, Pharmaceutical College, Central South University, Changsha, China.|College of Pharmacy, Xinxiang Medical University, Xinxiang, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: College of Basic Medical Sciences, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, China.|School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Yin
authors.affiliation: Sanqun Medical College, Xinxiang Medical University, Xinxiang, China.
authors.forename: Mo-Li
authors.initials: ML
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Pharmaceutical College, Central South University, Changsha, China.
authors.forename: Guo-Pin
authors.initials: GP
authors.lastname: Pan
authors.affiliation: Sanqun Medical College, Xinxiang Medical University, Xinxiang, China.
authors.forename: Fan-Rong
authors.initials: FR
authors.lastname: Zhao
authors.affiliation: School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.
authors.forename: Jun-Xiu
authors.initials: JX
authors.lastname: Lu
authors.affiliation: Department of Clinical Nutrition, The Affiliated Hospital, Hunan Normal University, Changsha, China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Xinxiang Medical University, Xinxiang, China.|The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Shuang-Xi
authors.initials: SX
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Pharmaceutical College, Central South University, Changsha, China.
authors.forename: Chang-Ping
authors.initials: CP
authors.lastname: Hu
mesh_terms: D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000378:metabolism; D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation; D060825:Cognitive Dysfunction / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008294:Malathion / Q000031:analogs & derivatives* / Q000633:toxicity; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D020768:Middle Cerebral Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010575:Pesticides / Q000633:toxicity*; D020769:Posterior Cerebral Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D051381:Rats; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D010575:Pesticides; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C549713:isocarbophos; D000110:Acetylcholinesterase; D000109:Acetylcholine; D008294:Malathion
keywords: ageing; endothelial dysfunction; organophosphorus; vascular cognitive impairment
references.citation: Toxicol Lett. 2012 Feb 25;209(1):86-93
references.pmid: 22155227
references.citation: Toxicology. 2014 Mar 20;317:1-5
references.pmid: 24447378
references.citation: Cochrane Database Syst Rev. 2013 Jan 31;(1):CD008900
references.pmid: 23440834
references.citation: Agents Actions. 1992 Jan;35(1-2):57-63
references.pmid: 1387283
references.citation: Cereb Cortex. 2015 Feb;25(2):423-32
references.pmid: 24008582
references.citation: Methods Find Exp Clin Pharmacol. 2000 Mar;22(2):89-95
references.pmid: 10849891
references.citation: Neuroscience. 2015 Apr 16;291:81-92
references.pmid: 25681520
references.citation: Eur J Med Chem. 2013;70:165-88
references.pmid: 24148993
references.citation: Int Neurourol J. 2013 Sep;17(3):114-20
references.pmid: 24143289
references.citation: Arch Environ Health. 1988 Jan-Feb;43(1):38-45
references.pmid: 3355242
references.citation: Environ Health Perspect. 2006 May;114(5):691-6
references.pmid: 16675422
references.citation: Environ Int. 2012 Nov 1;48:109-20
references.pmid: 22892382
references.citation: Neurotoxicology. 2015 May;48:9-20
references.pmid: 25704171
references.citation: Toxicology. 2014 Aug 1;322:1-13
references.pmid: 24801903
references.citation: Scand J Work Environ Health. 1998 Feb;24(1):18-29
references.pmid: 9562397
references.citation: J Med Toxicol. 2009 Dec;5(4):196-9
references.pmid: 19876851
references.citation: Front Aging Neurosci. 2013 Apr 10;5:17
references.pmid: 23596414
references.citation: Toxicol Lett. 2001 Mar 31;120(1-3):343-51
references.pmid: 11323193
references.citation: Int J Occup Environ Health. 2002 Jan-Mar;8(1):27-34
references.pmid: 11843437
references.citation: J Ethnopharmacol. 2009 Oct 29;126(1):134-42
references.pmid: 19665536
references.citation: J Neurol Sci. 2002 Nov 15;203-204:263-6
references.pmid: 12417395
references.citation: FASEB J. 2006 Aug;20(10):1733-5
references.pmid: 16807370
references.citation: Neuropathology. 2014 Apr;34(2):109-27
references.pmid: 24118348
references.citation: J Neurol Sci. 2014 Dec 15;347(1-2):66-77
references.pmid: 25266713
references.citation: Am J Public Health. 1994 May;84(5):731-6
references.pmid: 8179040
references.citation: Lancet. 1995 May 6;345(8958):1135-9
references.pmid: 7723544
references.citation: Lancet. 1991 Jul 27;338(8761):223-7
references.pmid: 1676786
references.citation: Can J Neurol Sci. 1986 Nov;13(4 Suppl):528-32
references.pmid: 3791067
references.citation: Lancet Neurol. 2002 Nov;1(7):426-36
references.pmid: 12849365
references.citation: Clin Biochem. 2008 Sep;41(13):1067-73
references.pmid: 18634772
references.citation: Brain Res Rev. 2007 Apr;54(1):162-80
references.pmid: 17296232
references.citation: Neuron. 2013 Nov 20;80(4):844-66
references.pmid: 24267647
references.citation: Fundam Appl Toxicol. 1997 May;37(1):95-9
references.pmid: 9193927