PLoS ONE：欧洲科学家首次发现提高大脑认知功能的机理

欧盟第七研发框架计划（FP7）资助290万欧元，由丹麦、西班牙和瑞士科学家组成的研究团队，在分子和细胞学研究方面取得重要进展，首次发现提高大脑认知功能的机理。该发现对治疗老年痴呆症、孤独症和各种精神失调疾病具有潜力，研究结果在最新一期的《公共科学图书馆生物学》PLoS Biology杂志上发表。

大脑中连接神经元的突融，对人类的认知功能起着举足轻重的关键作用，尤其是控制大脑认知功能活力的突融模式。婴儿出生时大脑神经元的突融连接并不是固定的，但突融连接对神经元强度和活力的反应明显。神经元的突融连接是动态的，并持续改变着神经元的强度和特性。这一过程在生物学上被称为突融可塑性（Synaptic Plasticity），突融可塑性形成大脑学习和记忆的细胞基础。研究团队进行的科学探索证实，人为地操作突融可塑性可以提高大脑的认知功能。

科研人员通过采集来自细胞到细胞信息联络的神经元蛋白被称作缩氨酸肽（Peptide）上的一枚小蛋白片断，制作成一枚更大的塑料状（Plastic-like）突融，新生成的突融（FGL）引发神经细胞的连锁反应，为突融可塑性提供了便利。FGL引起新神经传递素受体进入大脑海马（Hippocampus）区域的突融，从而对增加学习和记忆的多种方式产生积极作用，成为提高大脑认知功能和医治精神紊乱的有效手段。

doi:10.1371/journal.pbio.1001262
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Facilitation of AMPA Receptor Synaptic Delivery as a Molecular Mechanism for Cognitive Enhancement

Shira Knafo1,2#*, César Venero3#*, Cristina Sánchez-Puelles1, Inmaculada Pereda-Peréz3, Ana Franco4, Carmen Sandi5, Luz M. Suárez2,6, José M. Solís6, Lidia Alonso-Nanclares2, Eduardo D. Martín7, Paula Merino-Serrais2, Erika Borcel3, Shizhong Li8, Yongshuo Chen8, Juncal Gonzalez-Soriano9, Vladimir Berezin8, Elisabeth Bock8, Javier DeFelipe2, José A. Esteban1*

Cell adhesion molecules and downstream growth factor-dependent signaling are critical for brain development and synaptic plasticity, and they have been linked to cognitive function in adult animals. We have previously developed a mimetic peptide (FGL) from the neural cell adhesion molecule (NCAM) that enhances spatial learning and memory in rats. We have now investigated the cellular and molecular basis of this cognitive enhancement, using biochemical, morphological, electrophysiological, and behavioral analyses. We have found that FGL triggers a long-lasting enhancement of synaptic transmission in hippocampal CA1 neurons. This effect is mediated by a facilitated synaptic delivery of AMPA receptors, which is accompanied by enhanced NMDA receptor-dependent long-term potentiation (LTP). Both LTP and cognitive enhancement are mediated by an initial PKC activation, which is followed by persistent CaMKII activation. These results provide a mechanistic link between facilitation of AMPA receptor synaptic delivery and improved hippocampal-dependent learning, induced by a pharmacological cognitive enhancer.