Chinese Journal of Contemporary Neurology and Neurosurgery (Jun 2014)
Aggravation of spatial learning and memory impairment by type 2 diabetes mellitus in rats with chronic cerebral hypoperfusion and its possible mechanism
Abstract
Objective To explore whether type 2 diabetes mellitue (DM) aggravates the spatial learning and memory impairment in rats with chronic cerebral hypoperfusion (CCH) and the possible mechanism. Methods Twenty-four Sprague-Dawley (SD) rats were randomly divided into 4 groups: control group (normal diet + sham); DM group [high-fat diet + streptozocin (STZ) injection]; CCH group [normal diet + two vessel occlussion (2-VO)] and DM + CCH group (high-fat diet + STZ injection + 2-VO). All rats were submitted to behavioral testing for spatial learning and memory in Morris water maze test, and immunofluorescence staining to detect hippocampal β-site amyloid precursor protein cleaving enzyme 1 (BACE-1) positive cells. The relative expressions of BACE-1 in hippocampus were detected with Western blotting. Results Morris water maze test showed escape latency of DM + CCH group was significantly longer than control group on 2nd-5th days [(54.60 ± 3.75) s vs (25.99 ± 4.10) s, P = 0.000; (45.39 ± 2.78) s vs (27.50 ± 4.39) s, P = 0.003; (39.71 ± 3.47) s vs (20.34 ± 3.69) s, P = 0.001; (41.43 ± 4.48) s vs (11.35 ± 3.95) s, P = 0.000]. The percentage of target quadrant time in DM + CCH group on the 6th day was significantly reduced compared with the control group [(22.38 ± 3.41)% vs (43.69 ± 3.22)%, P = 0.000]. Compared with control group, BACE-1 positive cells significantly increased in the hippocampus of DM + CCH group, and the relative expression of BACE-1 increased statistically (0.23 ± 0.04 vs 0.06 ± 0.02, P = 0.005). Conclusions Type 2 diabetes mellitus exacerbates spatial learning and memory impairment of rats with chronic cerebral hypoperfusion, which may be related to the abnormal expression of BACE-1 in the hippocampus of rats. doi: 10.3969/j.issn.1672-6731.2014.06.010
