Chronic administration of isocarbophos induces vascular cognitive impairment in rats |
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Authors: | Peng Li Ya‐Ling Yin Mo‐Li Zhu Guo‐Pin Pan Fan‐Rong Zhao Jun‐Xiu Lu Zhan Liu Shuang‐Xi Wang Chang‐Ping Hu |
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Institution: | 1. Department of Pharmacology, Pharmaceutical College, Central South University, Changsha, China;2. College of Pharmacy, Xinxiang Medical University, Xinxiang, China;3. College of Basic Medical Sciences, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, China;4. School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China;5. Sanqun Medical College, Xinxiang Medical University, Xinxiang, China;6. Department of Clinical Nutrition, The Affiliated Hospital, Hunan Normal University, Changsha, China;7. The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China |
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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. |
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Keywords: | vascular cognitive impairment organophosphorus endothelial dysfunction ageing |
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