TRPC1介导海马内少突胶质细胞与有髓神经纤维损伤对糖尿病认知功能障碍作用的机制探讨

Diabetes have become an important risk of Alzheimer’s disease (AD), and it can accelerate the progression of AD. The mechanism underlying the cognitive dysfunction of diabetes is not fully understood. The previous studies mainly focused on the abnormalities of neurons and synapses, but there were few studies on the mylinated fibers. The clinical studies and animal studies indicated that there were obvious dmyelination injuries in thee white matter of diabetic patients, and there were AD-like pathological changes in he axons of the hippocampus in STZ-induced diabetic rat with encephhalophy. These studies sugggested that the deficits in the hippocampal myelinated nerve fibers might be involved in the cognitive function decline of diabetes. Howevever, it is unknown whether there is relationship between the myelin sheath deficits in hippocampus and the cognitive dysfunction in diabetes and what is the role that the oligodendrocytes play in the hippocampus. TRPC1 is an important calcium channel to regulate the differentiation of oligodendrocyte progenitor cells. Moreover, the expression of TRPC1 was decreased both in the diabetic patients and in diabetic animals. Thereforre, we speculated that TRPC1 might be related to hippcampus deficits in diabetes. In this project, we will investigate the changes of the myelinated nerve fibers and oligodendrocytes in STZ-induced diabetic hippocampus in order to figure out the relationship between the myelin sheath deficit and the cognitive dysfunction of diabetes. We will also explore the mechanism and roles that the oligodendrocytes play in the hippocampus of the STZ-induced diabetic rats through TRPC1. The results will provide new theoretical evidence for the treatment and prevention of the cogniton deficit of diabetes.

糖尿病已成为阿尔茨海默病（AD）的独立危险因素，可加速AD进展。而糖尿病认知功能障碍机制尚不十分明确。现研究主要集中于神经元及突触异常，对有髓神经纤维研究甚少。临床试验和动物模型研究均证实：糖尿病大脑白质存在明显脱髓鞘损伤，STZ模型大鼠海马轴突有AD样病理改变。这提示海马有髓神经纤维损伤很可能参与了糖尿病认知功能减退。但海马髓鞘损伤与糖尿病认知功能障碍之间到底有无关联性？少突胶质细胞在海马损伤中又起什么作用？ TRPC1是调控少突胶质前体细胞分化的关键钙通道，且在糖尿病患者和动物体内表达均明显下调。因此我们推测TRPC1可能与糖尿病海马损伤相关。本研究拟采用体视学方法定量STZ模型大鼠海马有髓神经纤维和少突胶质细胞的改变，以期明确髓鞘损伤与糖尿病认知功能障碍之间的关系。并以TRPC1为切入点，探讨少突胶质细胞在糖尿病有髓神经纤维损伤中的作用机制。为预防和治疗糖尿病认知功能障碍提供新信息。

糖尿病已成为阿尔茨海默病（AD）的独立危险因素，可加速AD进展。而糖尿病认知功能障碍机制尚不十分明确。现研究主要集中于神经元及突触异常，对有髓神经纤维研究甚少。临床试验和动物模型研究均证实：糖尿病大脑白质存在明显脱髓鞘损伤，STZ模型大鼠海马轴突有AD样病理改变。这提示海马有髓神经纤维损伤很可能参与了糖尿病认知功能减退。本研究采用体视学方法定量STZ模型大鼠海马有髓神经纤维和少突胶质细胞的改变，以期明确髓鞘损伤与糖尿病认知功能障碍之间的关系。本研究结果显示：认知功能减退早期，STZ成模大鼠海马及CA1和齿状回内神经元总数尽管有减少，但没有显著性差异；突触总数，及每神经元突触数量均显著下降。突触总数的显著性改变，可能与神经元功能减退、神经纤维减退有关。本研究结果为预防和治疗糖尿病认知功能障碍提供新信息。