EPISODIC-LIKE AND PROCEDURAL MEMORY IMPAIRMENTS IN HISTAMINE H1 RECEPTOR KNOCKOUT MICE COINCIDE WITH CHANGES IN ACETYLCHOLINE ESTERASE ACTIVITY IN THE HIPPOCAMPUS AND DOPAMINE TURNOVER IN THE CEREBELLUM
EPISODIC-LIKE AND PROCEDURAL MEMORY IMPAIRMENTS IN HISTAMINE H1 RECEPTOR KNOCKOUT MICE COINCIDE WITH CHANGES IN ACETYLCHOLINE ESTERASE ACTIVITY IN THE HIPPOCAMPUS AND DOPAMINE TURNOVER IN THE CEREBELLUM
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DOI：
10.1016/j.neuroscience.2008.09.025
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发表时间：
2008-12-02
期刊：
影响因子：
3.3
通讯作者：
De Souza-Silva, M. A.
中科院分区：
文献类型：
--
作者：
Dere, E.;Zlomuzica, A.;De Souza-Silva, M. A.
我们研究了组胺H1受体敲除（H1 RKO）小鼠的类情节记忆（ELM）和程序记忆（PM）。为了与可能的行为缺陷的神经生物学变化，我们研究了H1 R-KO和野生型（WT）小鼠的乙酰胆碱酯酶（AChE）的活性在海马和AChE和酪氨酸羟化酶（TH）的表达在纹状体的亚区域。此外，我们分析了乙酰胆碱（ACh），5-HT和多巴胺（DA）的水平，包括代谢产物，在小脑的H1 R-KO和WT小鼠。与杂合H1 R-KO和WT小鼠相比，纯合H1 R-KO小鼠显示ELM受损。纯合子H1 R-KO小鼠在ELM任务中的表现主要由基于熟悉度的记忆过程驱动。虽然纯合H1 R-KO小鼠在获得PM期间的表现与杂合H1 R-KO和WT小鼠相似，如用加速旋转棒测量的，但在7天的保留间隔后，其表现相对于杂合H1 R-KO和WT小鼠受损。这些发现表明，ELM和长期PM在纯合子H1 R-KO小鼠中受损。神经化学分析表明，H1 R-KO小鼠有显着较低水平的AChE活性在齿状回（DG）和海马CA 1亚区与WT小鼠相比。纯合H1 R-KO小鼠还显示小脑中二羟基苯乙酸（DOPAC）水平显著降低和DOPAC/DA比率降低，表明纯合H1 R-KO小鼠小脑中的DA周转减慢。总之，纯合子H1 R-KO小鼠表现出严重的长期记忆缺陷，无论是，ELM和PM，这与在海马AChE活性的变化，以及在小脑DA营业额。这些发现的重要性阿尔茨海默氏症（AD）和帕金森氏病（PD）进行了讨论。(C)2008年IBRO。由爱思唯尔有限公司出版。保留所有权利。
We investigated episodic-like (ELM) and procedural memory (PM) in histamine H1 receptor knockout (H1RKO) mice. In order to relate possible behavioral deficits to neurobiological changes, we examined H1R-KO and wildtype (WT) mice in terms of acetylcholine esterase (AChE) activity in subregions of the hippocampus and AChE and tyrosine hydroxylase (TH) expression in the striatum. Furthermore, we analyzed acetylcholine (ACh), 5-HT and dopamine (DA) levels, including metabolites, in the cerebellum of H1R-KO and WT mice. The homozygous H1R-KO mice showed impaired ELM as compared with the heterozygous H1R-KO and WT mice. The performance of homozygous H1R-KO mice in the ELM task was primarily driven by familiarity-based memory processes. While the homozygous H1R-KO mice performed similar to the heterozygous H1R-KO and WT mice during the acquisition of a PM, as measured with an accelerating rotarod, after a retention interval of 7 days their performance was impaired relative to the heterozygous H1R-KO and WT mice. These findings suggest that, both, ELM and long-term PM are impaired in the homozygous H1R-KO mice. Neurochemical assays revealed that the H1R-KO mice had significantly lower levels of AChE activity in the dentate gyrus (DG) and CA1 subregions of the hippocampus as compared with the WT mice. The homozygous H1 R-KO mice also displayed significantly reduced dihydroxy-phenylacetic acid (DOPAC) levels and a reduced DOPAC/DA ratio in the cerebellum, suggesting that the DA turnover in the cerebellum is decelerated in homozygous H1R-KO mice. In conclusion, homozygous H1R-KO mice display severe long-term memory deficits in, both, ELM and PM, which coincide with changes in AChE activity in the hippocampus as well as DA turnover in the cerebellum. The importance of these findings for Alzheimer's (AD) and Parkinson's disease (PD) is discussed. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.