Antisense knockdown of drebrin A, a dendritic spine protein, causes stronger preference, impaired pre-pulse inhibition, and an increased sensitivity to psychostimulant
Antisense knockdown of drebrin A, a dendritic spine protein, causes stronger preference, impaired pre-pulse inhibition, and an increased sensitivity to psychostimulant
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DOI：
10.1016/j.neures.2004.02.014
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发表时间：
2004-06-01
影响因子：
2.9
通讯作者：
Saji, M
中科院分区：
文献类型：
--
作者：
Kobayashi, R;Sekino, Y;Saji, M
位于树突棘中的 Drebrin 调节其形态变化，并通过树突棘功能在突触可塑性中发挥作用。在阿尔茨海默病或唐氏综合症患者的大脑中发现了减少的drebrin。为了检查drebrin蛋白水平的下调是否会导致高级脑功能（例如记忆或认知）缺陷，我们使用日本血凝病毒（HVJ）脂质体基因转移技术对大鼠大脑中的drebrin A表达进行反义诱导敲低。我们研究了drebrin体内敲低对水迷宫任务中的空间记忆、预脉冲抑制测试中的感觉运动门控、开放场测试中的适应性行为以及安非他明诱导的运动反应中对精神兴奋剂的敏感性的影响。体内drebrin A敲低的大鼠由于持续行为、前脉冲抑制（PPI）受损、运动活动增加、焦虑样行为以及对精神兴奋剂的敏感性增加而表现出对先前事件的更强偏好，表明这些行为与精神分裂症相关。这些发现表明，减少的树突蛋白会导致认知功能缺陷，但不会导致空间记忆缺陷，这可能是通过树突棘功能减退所致。 (C) 2004 Elsevier Ireland Ltd 和日本神经科学学会。版权所有。
Drebrin located in dendritic spines regulates their morphological changes and plays a role in the synaptic plasticity via spine function. Reduced drebrin has been found in the brain of patients with Alzheimer's disease or Down's syndrome. To examine whether the down-regulation of drebrin protein levels causes deficits in higher brain function, such as memory or cognition, we performed antisense-induced knockdown of drebrin A expression in rat brain using an hemagglutinating virus of Japan (HVJ)-liposome gene transfer technique. We investigated the effects of drebrin in vivo knockdown on spatial memory in a water-maze task, sensorimotor gating in a pre-pulse-inhibition test, adaptive behaviors in an open-field test, and sensitivity to psychostimulant in an amphetamine-induced locomotor response. Rats with drebrin A in vivo knockdown displayed a stronger preference for a previous event due to perseverative behavior, impaired pre-pulse inhibition (PPI), increased locomotor activity, anxiety-like behavior, and an increased sensitivity to psychostimulant, suggesting behaviors related to schizophrenia. These findings indicated that decreased drebrin produces deficits in cognitive function but not in spatial memory, probably via hypofunction of dendritic spines. (C) 2004 Elsevier Ireland Ltd and The Japan Neuroscience Society. All rights reserved.