Huang Freesia L, Huang Kuo-Ping, Boucheron Catherine
Developmental Neuroscience Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-4510, USA.
Learn Mem. 2007 Aug 1;14(8):512-9. doi: 10.1101/lm.636107. Print 2007 Aug.
Neurogranin (Ng), a PKC substrate, is abundantly expressed in brain regions important for cognitive functions. Deletion of Ng caused severe deficits in spatial learning and LTP in the hippocampal CA1 region of mice. These Ng-/- mice also exhibit deficits in the amplification of their hippocampal signaling pathways critical for learning and memory. A short-term exposure to an enriched environment failed to improve their behavioral performances. Here, we showed that a long-term enrichment protocol for the aging mice was beneficial to the Ng-/- as well as Ng+/+ and Ng+/- mice in preventing age-related cognitive decline. Enrichment also caused an increase in the hippocampal CREB level of all three genotypes and Ng level of Ng+/+ and Ng+/- mice, but not that of alphaCaMKII or ERK. Interestingly, hippocampal slices of these enriched aging Ng-/- mice, unlike those of Ng+/+ and Ng+/- mice, did not show enhancement in the high frequency stimulation (HFS)-induced LTP in the CA1 region. It appears that the learning and memory processes in these enriched aging Ng-/- mice do not correlate with the HFS-induced LTP, which is facilitated by Ng. These results demonstrated that long-term enrichment for the aging Ng-/- mice may improve their cognitive function through an Ng-independent plasticity pathway.
神经颗粒素（Ng）是一种蛋白激酶C（PKC）底物，在对认知功能至关重要的脑区中大量表达。Ng基因缺失导致小鼠海马CA1区的空间学习和长时程增强（LTP）出现严重缺陷。这些Ng基因敲除（Ng-/-）小鼠在对学习和记忆至关重要的海马信号通路放大方面也表现出缺陷。短期暴露于丰富环境未能改善它们的行为表现。在此，我们表明，针对衰老小鼠的长期丰富环境方案对Ng-/-以及Ng+/+和Ng+/-小鼠预防与年龄相关的认知衰退有益。丰富环境还导致所有三种基因型小鼠的海马环磷腺苷反应元件结合蛋白（CREB）水平升高，以及Ng+/+和Ng+/-小鼠的Ng水平升高，但α-钙/钙调蛋白依赖性蛋白激酶II（alphaCaMKII）或细胞外信号调节激酶（ERK）水平未升高。有趣的是，与Ng+/+和Ng+/-小鼠不同，这些处于丰富环境中的衰老Ng-/-小鼠的海马切片在高频刺激（HFS）诱导的CA1区长时程增强中未表现出增强。看来，这些处于丰富环境中的衰老Ng-/-小鼠的学习和记忆过程与由Ng促进的HFS诱导的LTP不相关。这些结果表明，对衰老的Ng-/-小鼠进行长期丰富环境处理可能通过一条不依赖Ng的可塑性途径改善其认知功能。
