老年性学习记忆减退与大鼠脑发育过程中周期素依赖性蛋白激酶5的表达

背景周期素依赖性蛋白激酶5是周期素依赖性蛋白激酶家族的成员之一,脑发育过程中周期素依赖性蛋白激酶5mRNA及其蛋白在脑内的表达及分布状况与神经退行性变思维认知学的关系一直被研究者关注.目的探讨大脑发育过程中的周期素依赖性蛋白激酶5对神经系统的发生和退行性变的影响.设计单因素方差分析实验.单位解放军第一军医大学组织学与胚胎学教研室和神经生物学教研室.材料实验在解放军第三军医大学组织学与胚胎学实验室完成.Wistar大鼠胚胎期(E8～E21)、新生期(P0～P15)、幼年期(P16～2个月)、成年期(＞ 2个月)及老年期(＞8个月后)5个阶段25只大鼠,每组5只.方法采用胚胎期至老年期大鼠脑片行原位杂交组织化学和免疫细胞化学染色.主要观察指标不同脑区内周期素依赖性蛋白激酶5mRNA及其蛋白的阳性细胞分布及表达状况.结果25只大鼠全部进入结果分析.①周期素依赖性蛋白激酶5mRNA在大鼠E14～P350整个发育过程中均有表达,成年后趋于稳定;周期素依赖性蛋白激酶5mRNA主要定位于神经元,阳性区域主要分布于大脑皮质、海马、丘脑、下丘脑、小脑及部分神经核团.②出生后周期素依赖性蛋白激酶5表达较强,胚胎及老年鼠表达较弱;阳性区域集中在室周区、海马、小脑及部分神经核团内;老年鼠仅在海马、小脑蒲肯野细胞层内表达.结论脑内周期素依赖性蛋白激酶5的作用贯穿了整个神经发育的各个时期,在新生期、幼年期有较为显著的表达,成年后表达下降,尤以老年期显著.老年大鼠海马内周期素依赖性蛋白激酶5的表达下调可能与老年性学习记忆减退的发生密切相关.

Decline of learning and memory in senility and expression of cyclin-dependent kinase-5 in brain development of rats

BACKGROUND: Cyclin-dependent kinase-5 (CDK-5) is one of the members in cyclin-dependent protein kinase family. The attention has being drawn by researchers on the relationship between the expression and distribution of CDK-5 mRNA and its protein in the brain during brain development and neural degeneration in thought-cognition.OBJECTIVE: To probe into the influence of CDK-5 on neurogeny and neural degeneration during cerebral development.DESIGN: Single factor analysis of variance.SETTING: Histological and Embryological Department and Neurobiological Department in Third Military Medical University of Chinese PLA.MATERIALS: The experiment was performed in Histological and Embryological Department and Neurobiological Department in Third Military Medical University of Chinese PLA. Twenty-five Wistar rats of 5 phases were employed, named embryonicphase (E8-E21), neonatal phase (P0-P15),childhood (P16-2 months), grown-up phase (＞ 2 months) and senile phase (＞ 8 months), 5 rats in each group.METHODS: In situ hybridization histochemistry (ISH) and immunohistochemistry (IHC) staining was adopted in brain sections from embryonic phase to senile phase.MAIN OUTCOME MEASURFS: Distribution and expression of positive cells of CDK-5 mRNA and protein in various brain areas.RESULTS: Twenty-five rats entered result analysis for all. ① The expression of CDK-5 mRNA presented in entire development from E14 to P350and was in tendency of stability after growth-up. CDK-5 mRNA localized mainly in neurons and positive regions distributed mainly in cerebral cortex, hippocampus, thalamus, hypothalamus, cerebellum and a part of nerve nuclei. ② The expression of CDK-5 was strong after birth and it was weaker in embryonic and senile rats. Positive regions concentrated mainly in peripheral ventricle, hippocampus, cerebellum and a part of nerve nuclei.The expression only presented in hippocampus and Purkinje cellular layer of cerebellum in senile rats.CONCLUSION: CDK-5 in brain runs through entire phases of neural development, it expresses more significantly in neonatal phase and childhood and declines after growth-up, especially in senile phase. The declined expression of CDK-5 in hippocampus of senile rats is closely associated with decline of learning and memory in senility probably.