Chronic administration of isocarbophos induces vascular cognitive impairment in rats

• Published in: Journal of cellular and molecular medicine 2016-04, Vol.20 (4), p.731-739
• Main Authors: Li, Peng, Yin, Ya‐Ling, Zhu, Mo‐Li, Pan, Guo‐Pin, Zhao, Fan‐Rong, Lu, Jun‐Xiu, Liu, Zhan, Wang, Shuang‐Xi, Hu, Chang‐Ping
• Format: Article
• Language: English
• Subjects: Acetylcholine - antagonists & inhibitors; Acetylcholine - metabolism; Acetylcholinesterase; Acetylcholinesterase - genetics; Acetylcholinesterase - metabolism; ageing; Alzheimer's disease; Animals; Astrocytes; Astrocytes - drug effects; Astrocytes - metabolism; Astrocytes - pathology; Brain research; Cerebrovascular Circulation; Cerebrovascular diseases; Cognitive ability; Cognitive Dysfunction - chemically induced; Cognitive Dysfunction - genetics; Cognitive Dysfunction - metabolism; Cognitive Dysfunction - pathology; Correlation analysis; Dementia; Dementia disorders; Electron microscopy; endothelial dysfunction; Experiments; Gene Expression; Hippocampus; Hippocampus - blood supply; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Impairment; Injury analysis; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Learning; Light microscopy; Liver; Malathion - analogs & derivatives; Malathion - toxicity; Maze Learning - drug effects; Memory; Memory - drug effects; Metabolism; Microscopy; Middle Cerebral Artery - drug effects; Middle Cerebral Artery - metabolism; Middle Cerebral Artery - pathology; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; organophosphorus; Original; Pesticides; Pesticides - toxicity; Plasma; Poisoning; Posterior Cerebral Artery - drug effects; Posterior Cerebral Artery - metabolism; Posterior Cerebral Artery - pathology; Primary Cell Culture; Rats; Rodents; Structure-function relationships; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - metabolism; vascular cognitive impairment; Vascular dementia; Veins & arteries
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.12775

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.