Altered expression of MAP-2, GAP-43, and synaptophysin in the hippocampus of rats with chronic cerebral hypoperfusion correlates with cognitive impairment.
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.
Liu
Han-Xing
HX
Department of Neurology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China.
Zhang
Jun-Jian
JJ
Zheng
Ping
P
Zhang
Yi
Y
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*
D019922:GAP-43 Protein; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D016708:Synaptophysin