title: Altered expression of MAP-2, GAP-43, and synaptophysin in the hippocampus of rats with chronic cerebral hypoperfusion correlates with cognitive impairment.
abstract: Chronic cerebral hypoperfusion causes cognitive impairment, but the underlying molecular mechanism is not well understood. We used permanent occlusion of bilateral common carotid arteries (2-VO) to induce chronic cerebral hypoperfusion in male Wistar rats. Cognitive impairment and the expression patterns of MAP-2, GAP-43, and synaptophysin were examined. We found that both learning capacity and memory were gradually impaired in the rats with chronic cerebral hypoperfusion concomitant with increased duration of 2-VO treatment. Four weeks of 2-VO treatment resulted in down-regulation of synaptophysin expression at the protein levels, and a further decrease was observed at 10-20 weeks, although mRNA levels remained the same. Ten weeks of 2-VO treatment lead to down-regulation of MAP-2 expression at both the mRNA and protein levels with a further decrease at 20 weeks. Interestingly, GAP-43 mRNA was significantly up-regulated by 2-VO treatment, although the protein levels were not altered. Therefore, the cognitive impairment caused by chronic cerebral hypoperfusion may be partially explained by reduced expression of synaptophysin and MAP-2 at the protein level. The reduction in MAP-2 expression may be attributed to the inhibition of transcription, while the reduction in synaptophysin expression might be due to the inhibition of translation. Up-regulation of GAP-43 mRNA in the rat hippocampus with 2-VO treatment suggests that a compensatory mechanism may antagonize ischemic challenges.
authors.affiliation: Department of Neurology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China.
authors.forename: Han-Xing
authors.initials: HX
authors.lastname: Liu
authors.forename: Jun-Jian
authors.initials: JJ
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003072:Cognition Disorders / Q000378:metabolism*; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013223:Statistics as Topic; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism*
chemical_list: D019922:GAP-43 Protein; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D016708:Synaptophysin