Objective: To investigate the Influence of chronic cerebral hypoperfusion on gap junction ultrastructure and expression of connexin (Cx)36, Cx32, and Cx26 in hippocampus the microstructure of gap junction and the expression of gap junction subunits in the hippocampus of cognition impaired animals. Cognition impairment was induced by the permanent occlusion of the carotid arteries (2-VO).
Methods: Twenty-seven Wistar rats underwent two-vessel occlusion (2-VO, ligation of bilateral common carotid arteries) and then were randomly divided into 2 equal groups: 2-VO 3 week, 2-VO 8 week and 2-VO 12 week groups to undergo Morris water maze test 3, 8, and 12 weeks later to observe the spatial learning and memory ability. Another 9 rats underwent sham operation to be used as control group. After Morris water maze test the rats were killed. The brains were taken out from 3 rats from each group to undergo thin-section transmission electron microscopy to observe the ultrastructure of the gap junctions in the CA1 area of hippocampus. RT-PCR and Western blotting were used to detect the mRNA and protein expression of Cx 36, Cx32, and Cx26 in the hippocampus of the other 27 rats, 6 from each group.
Results: Compared to the control group, the density of cytomembrane of gap junction was lower, the interspace of gap junction were larger in the 2-VO 3 week group, and these abnormalities were gradually improved in the 2-VO 8 and 12 week groups. The mRNA and protein levels of Cx36 and Cx32 of the three 2-VO groups were the lowest in the 2-VO 3 week group, and then gradually increased, however, all significantly lower than those of the control group (all P < 0.05). The mRNA level of Cx26 was not altered significantly, while the protein expression levels of Cx26 in the three 2-VO groups were all higher compared with the control group (all P < 0.05).
Conclusion: The altered neuronal gap junction may participate in the cognition impairment caused by chronic cerebral hypoperfusion.