Protective effects of low dose minocycline on spatial learning and memorizing ability and the expression of PSD-95 in rats after focal cerebral ischemia reperfusion

Abstract:

Objective：To investigate the effects of low dose minocycline through vein on the spatial learning and memorizing ability and the expressions of growth associated protein-43（GAP-43） and postsynaptic density 95（PSD-95） in ischemic hippocampus of rats after focal cerebral ischemia/reperfusion（I/R）. Methods：The middle cerebral artery occlusion procedure was used to induce focal cerebral ischemia. Forty-five adult male Sprague-Dawley rats were randomly divided into sham-operated，I/R and minocycline groups. The GAP-43 and PSD-95 protein expression in ischemic hippocampus was measured by Western blot and immunohistochemistry，re－spectively. Morris water maze test was performed to detect the praxiology of rats after 2 weeks. Results：Compared with those in sham group，expression of GAP-43（0.49±0.03） and PSD-95（0.92±0.04） was significantly increased（P=0.000），escape latency was ex－tended（44.2±10.0） s，times of crossing the platform（2.6±0.9） and time percentage of swimming in target quadrant[（19.2±2.1）%，P=0.000] were significantly decreased in I/R group. Moreover，the rats in minocycline group demonstrated better spatial memory peformance than I/R group. The protein levels of GAP-43（0.72±0.05） was increased，PSD-95 was decreased（0.67±0.05，P=0.000），escape latency was shortened[（30.8±7.6） s，P=0.020]，times of crossing the platform（4.4±1.1，P=0.012） and time percentage of swimming in target quadrant[（30.4±2.7）%，P=0.000] were significantly decreased in minocycline group compared with those in I/R group（P=0.000）. Conclusion：Low dose intravenous minocycline improves the ability of learning and memorizing of rats after cerebral ischemia reperfusion，which may be partly associated with up-regulating GAP-43 and down-regulating PSD-95 pro－tein expression.