糖尿病早期小鼠初级视皮层受损与功能异常情况OA

Objective To investigate morphological and functional neural network alterations in the primary visual cortex(V1)during early-stage diabetes.Methods 32 SPF male C57BL/6J mice were randomly divided into con-trol and diabetic groups(n=16).Type 1 diabetes was induced by intraperitoneal injection of streptozotocin(STZ),with model validation via oral glucose tolerance test(OGTT)at week 4.Nissl staining was used to assess morpho-logical changes in brain slices of the two groups.Immunohistochemistry was performed to detect the expression of calcium/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)and somatostatin(SST)in the V1 area.The co-localization density of SST-positive signals on CaMKⅡ+neurons was then quantified by ImageJ software.In vivo electrophysiology was used for studying neuronal firing and functional connectivity.Results Compared with the control mice,nissl staining showed diabetic mice exhibited significant V1 thinning(P=0.02),reduced neuronal density(P=0.01).Immunohistochemistry found decreased SST integral optical density(P=0.02)and elevated mean fluorescence intensity(P=0.01),and lower SST density on CaMKⅡ+neurons in the diabetic group than in the control group.Compared with the control mice,in vivo electrophysiology studies indicated that diabetic mice showed reduced action potential peak-to-trough ratio and the absolute values of slope(P<0.01),as well as impaired functional connectivity,including conditional firing,mutual information,and Granger causality(P<0.000 1).Con-clusion Early diabetes induces V1 structural atrophy accompanied by SSTergic system disruption and multi-level functional degradation from single neurons to neural networks.