VALPROIC ACID REDUCES SPATIAL WORKING MEMORY AND CELL PROLIFERATION IN THE HIPPOCAMPUS
VALPROIC ACID REDUCES SPATIAL WORKING MEMORY AND CELL PROLIFERATION IN THE HIPPOCAMPUS
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DOI：
10.1016/j.neuroscience.2009.11.073
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发表时间：
2010-03-10
期刊：
影响因子：
3.3
通讯作者：
Wigmore, P. M.
中科院分区：
文献类型：
--
作者：
Umka, J.;Mustafa, S.;Wigmore, P. M.
丙戊酸（VPA）作为抗惊厥药和情绪稳定剂在临床上广泛使用，但是，也已知其通过抑制组蛋白脱乙酰酶的能力来阻断细胞增殖。已有大量服用VPA的患者出现认知障碍的报告。在这项研究中，我们研究了认知与海马内细胞增殖变化之间的关系，海马是一个大脑区域，新神经元的持续形成与学习和记忆有关。通过腹腔注射丙戊酸钠处理大鼠，降低了海马内齿状回颗粒下层的细胞增殖。这与他们进行校园依赖性空间记忆测试（新物体定位）的能力显著受损有关。此外，药物治疗导致海马内脑源性神经营养因子（BDNF）和Notch 1水平显著降低，但不导致doublecortin水平降低。这些结果支持VPA可能导致认知障碍的观点，并通过减少海马内的神经发生提供了可能的机制。(C)2010年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Valproic acid (VPA) is widely used clinically, as an anticonvulsant and mood stabilizer but is, however, also known to block cell proliferation through its ability to inhibit histone deacetylase enzymes. There have been a number of reports of cognitive impairments in patients taking VPA. In this investigation we examined the relationship between cognition and changes in cell proliferation within the hippocampus, a brain region where continued formation of new neurons is associated with learning and memory. Treatment of rats by i.p. injection of VPA, reduced cell proliferation in the sub granular zone of the dentate gyrus within the hippocampus. This was linked to a significant impairment in their ability to perform a hippocampus-dependent spatial memory test (novel object location). In addition, drug treatment caused a significant reduction in brain-derived neurotrophic factor (BDNF) and Notch 1 but not doublecortin levels within the hippocampus. These results support the idea that VPA may cause cognitive impairment and provide a possible mechanism for this by reducing neurogenesis within the hippocampus. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.