Gómez-Pinilla F, So V, Kesslak J P
Department of Physiological Science, UCLA, Los Angeles, CA 90095-1527, USA.
Brain Res. 2001 Jun 15;904(1):13-9. doi: 10.1016/s0006-8993(01)02394-0.
We report that rats learning a spatial memory task in the Morris water maze show elevated expression of the signal transduction receptor for BDNF and the synaptic associated protein synapsin I in the hippocampus. Nuclease protection assays showed maximal levels of TrkB and synapsin I mRNAs in the hippocampus by the time that asymptotic learning performance had been reached (Day 6). Increases in synapsin I mRNA were matched by changes in synapsin I protein as revealed by western blot analysis. Synapsin I is a downstream effector for the BDNF tyrosine kinase cascade pathway which has important roles in synaptic remodeling and function. Therefore, parallel changes in TrkB and synapsin I mRNAs suggest a role of the BDNF system in synaptic function or adaptation. Levels of TrkB mRNA in the hippocampus were attenuated after learning acquisition (Day 20), but synapsin I mRNA was still elevated, suggesting that the BDNF system may participate in events secondary to learning, such as strengthening of neural circuits. TrkB and synapsin I mRNAs showed an increasing trend in the cerebellum of learning rats and no changes were observed in the caudal cerebral cortex. The selectivity of the changes in trkB and synapsin I, affecting the hippocampus, is in agreement with the role of this structure in processing of spatial information. Behavioral regulation of neurotrophins may provide a molecular basis for the enhanced cognitive function associated with active lifestyles, and guide development of strategies to promote neural healing after CNS injury or disease.
我们报告称，在莫里斯水迷宫中学习空间记忆任务的大鼠，其海马体中脑源性神经营养因子（BDNF）的信号转导受体及突触相关蛋白突触素I的表达升高。核酸酶保护分析显示，在达到渐近学习表现时（第6天），海马体中TrkB和突触素I的mRNA水平达到最高。蛋白质印迹分析表明，突触素I mRNA的增加与突触素I蛋白的变化相匹配。突触素I是BDNF酪氨酸激酶级联途径的下游效应器，在突触重塑和功能中起重要作用。因此，TrkB和突触素I mRNA的平行变化表明BDNF系统在突触功能或适应性方面发挥作用。学习获得后（第20天），海马体中TrkB mRNA水平降低，但突触素I mRNA仍升高，这表明BDNF系统可能参与学习后的继发事件，如神经回路的强化。学习大鼠的小脑内TrkB和突触素I mRNA呈上升趋势，而在大脑尾状皮质未观察到变化。trkB和突触素I变化的选择性影响海马体，这与该结构在空间信息处理中的作用一致。神经营养因子的行为调节可能为与积极生活方式相关的认知功能增强提供分子基础，并指导促进中枢神经系统损伤或疾病后神经愈合策略的制定。
