Spatial memory impairment is related to the neuronal apoptosis in the CA1 region of the hippocampus and the acetylcholine release in the rat model of vascular dementia / 国际脑血管病杂志

ABSTRACT

Objective To investigate the correlations between the hippocampal acetylcholine (ACh) content and neuronal apoptosis in the hippocampal CA1 region as well as the spatial memory impairment in a rat model of vascular dementia (VaD).Methods Forty male healthy Sprague-Dawley rats were randomly divided into either a VaD group or a sham operation group (n =20 in each group).A VaD model was induced by intermittently clipping common carotid artery.Microdialysis was used to collect dialysis solutions in rat hippocampus.High-performance liquid chromatographic analysis was used to detect the ACh content in the dialysis fluid.Morris water maze test was used to test their learning and memory abilities.TUNEL staining was used to detect neuronal apoptosis in the hippocampal CA1 region.Results Microdialysis analysis showed that the ACh content in the hippocampus in the VaD group was significantly lower than that in the sham operation group (0.442 ± 0.028 μmmol/L vs.1.560 ± 0.092 μ mmol/L; t =51.697,P =0.000).TUNEL staining showed that the apoptosis rate in the hippocampal CA1 region in the VaD group was significantly higher than that in the sham operation group (55.652％ ±2.051％ vs.6.530％ ± 1.872％ ; t =79.114,P=0.000).The escape latencies at different detection time points were prolonged significantly (At day 349.713 ± 18.161 s vs.13.322 ± 2.454 s; t =-8.881,P =0.000; at day 434.368 ± 7.424 s vs.10.503±1.415 s; t=-14.121,P=0.000; at day 530.676± 6.669s vs.7.311± 1.534 s; t=-15.270,P =0.000),and the numbers of cross platform were reduced significantly (3.768 ± 1.072 vs.10.218 ± 1.165; t =18.224,P=0.000).Pearson correlation analysis showed that the ACh contents in the VaD group were negatively correlated with the escape latencies (at day 3r =-0.476,P =0.034; at day 4r=-0.700,P=0.001; at day 5r=-0.693,P=0.001).They were positively correlated with the numbers of cross platform (r =0.689,P =0.001),and negatively correlated with the neuronal apoptosis rates in the hippocampal CA1 region (r =-0.271,P =0.031).Conclusions The decreased ACh content,the increased neuronal apoptosis rate in the rat hippocampal CA1 region in the VaD model may be one of the mechanisms of cognitive impairment in VaD rats.