Yamada Kentaro, Matsukawa Noriyuki, Yuasa Hiroyuki, Hattori Manabu, Nakazawa Hideka, Borlongan Cesario V, Ojika Kosei
Department of Neurology and Neuroscience, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Aichi, Japan.
Brain Res. 2007 Jul 16;1158:169-75. doi: 10.1016/j.brainres.2007.05.013. Epub 2007 May 18.
Hippocampal cholinergic neurostimulating peptide (HCNP), originally isolated from soluble fraction of young rat hippocampus and released from hippocampus by the stimulation of N-methyl-d-aspartate (NMDA) receptors, enhances the cholinergic phenotype development in vitro. HCNP precursor protein (HCNP-pp) has multiple functions, not only acting as the precursor of HCNP but also serving as an inhibitor of phosphorylation of Erk and contributing to neuronal growth and memory formation. In this study, the accumulation of HCNP and/or HCNP precursor in hippocampus was found to progress from 2 to 5 months of age in senescence-accelerated mouse-prone 8 (SAM P8). This HCNP surge in the hippocampus appears to correspond to the age of onset of memory deterioration, reduction of amount of NMDA-type receptor, and morphological aberration in this dementia model mouse, SAM P8. The present findings, together with our previously published results, suggest that the HCNP and/or HCNP precursor is involved in the dysfunction of the cholinergic neuronal system and memory deterioration in this model mouse via NMDA-type receptor signaling and the activation of the MAP cascade.
海马胆碱能神经刺激肽（HCNP）最初从幼鼠海马的可溶性部分中分离出来，并通过N-甲基-D-天冬氨酸（NMDA）受体的刺激从海马中释放出来，它能在体外增强胆碱能表型的发育。HCNP前体蛋白（HCNP-pp）具有多种功能，不仅作为HCNP的前体，还作为细胞外调节蛋白激酶（Erk）磷酸化的抑制剂，并有助于神经元生长和记忆形成。在本研究中，发现衰老加速小鼠8（SAM P8）从2月龄到5月龄时海马中HCNP和/或HCNP前体的积累不断增加。海马中这种HCNP的激增似乎与该痴呆模型小鼠SAM P8中记忆衰退的起始年龄、NMDA型受体数量的减少以及形态学异常相对应。目前的研究结果与我们之前发表的结果共同表明，HCNP和/或HCNP前体通过NMDA型受体信号传导和丝裂原活化蛋白激酶（MAP）级联反应的激活，参与了该模型小鼠胆碱能神经系统功能障碍和记忆衰退过程。
