Diabetes mellitus (DM) may give rise to cognitive impairment, but the pathological mechanism involved was still unknown. We employed streptozotocin (STZ)-induced diabetic rats and test their capacity for learning and memory by three-arm radial maze. We determined the expression level of growth-associated protein-43 (GAP-43) and mitogen activated protein kinase phosphatase-1 (MKP-1) in the hippocampus by immunohistochemistry. MKP-1 mRNA level in the CA1 and dentate gyrus (DG) Hippocampal area is further determined by RT-PCR method. We also observed the ultrastructures of Hippocampal neurons by transmission electron microscopy (TEM). All data were analyzed by the independent samples t-test. Four weeks after STZ induction, the diabetic rats showed decreased capacity for learning and memory as indicated by the increase in the error number and reaction time in three-arm radial maze test. TEM results showed the ultrastructures of diabetic hippocampus, including area CA1 and DG, neurons were characterized by swollen mitochondria, increased heterochromatin accumulation and reduced synaptic contacts. The optical density as well as the positive neuron number for GAP-43 and MKP-1 decreased significantly in the CA1 and DG Hippocampal area in diabetic rats (P<0.01). RT-PCR results also showed MKP-1 mRNA in the CA1 and DG Hippocampal area was decreased in the diabetic rats. These results indicated that DM could down-regulate GAP-43 and MKP-1 expression in Hippocampal area that is in charge of memory and cognition. As indicated by our study, the changes in GAP-43 and MKP-1 expression in hippocampus may play a role in the pathogenesis of diabetic dementia.

译文

:糖尿病(DM)可能引起认知障碍,但涉及的病理机制仍不清楚。我们采用了链脲佐菌素(STZ)诱导的糖尿病大鼠,并通过三臂radial骨迷宫测试了它们的学习和记忆能力。我们通过免疫组织化学测定了海马中的生长相关蛋白43(GAP-43)和有丝分裂原活化蛋白激酶磷酸酶1(MKP-1)的表达水平。通过RT-PCR方法进一步测定CA1和齿状回(DG)海马区中的MKP-1 mRNA水平。我们还通过透射电子显微镜(TEM)观察了海马神经元的超微结构。所有数据均通过独立样本t检验进行分析。诱导STZ后四周,糖尿病大鼠的学习和记忆能力下降,这是通过三臂放射状迷宫测试中错误数和反应时间的增加来表明的。 TEM结果显示,糖尿病海马的超微结构包括CA1区和DG区,神经元的特征在于线粒体肿胀,异染色质积累增加和突触接触减少。糖尿病大鼠CA1区和DG海马区的GAP-43和MKP-1的光密度以及阳性神经元数量均显着下降(P <0.01)。 RT-PCR结果还显示,糖尿病大鼠CA1和DG海马区的MKP-1 mRNA降低。这些结果表明DM可以下调负责记忆和认知的海马区GAP-43和MKP-1的表达。正如我们的研究所表明的,海马区GAP-43和MKP-1表达的变化可能在糖尿病性痴呆的发病机理中起作用。

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