Mouse strain-specific nicotinic acetylcholine receptor expression by inhibitory interneurons and astrocytes in the dorsal hippocampus
Mouse strain-specific nicotinic acetylcholine receptor expression by inhibitory interneurons and astrocytes in the dorsal hippocampus
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DOI：
10.1002/cne.10943
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发表时间：
2004-01-12
影响因子：
2.5
通讯作者：
Rogers, SW
中科院分区：
文献类型：
--
作者：
Gahring, LC;Persiyanov, K;Rogers, SW
个体对尼古丁的反应可能反映了这种化合物与靶向nAChR的相互作用。然而，解决不同的遗传背景如何有助于独特的小鼠品系特异性反应，这种化合物仍然是一个重要的和未解决的问题。为了详细研究这个问题，使用免疫组织化学法测量了小鼠品系或品系BALB/c、C3 H/J、C57 BL/6、CBA/J、DBA/2、长睡眠（LS）、短睡眠（SS）和CF 1背侧海马中尼古丁乙酰胆碱受体（nAChR）亚单位α 3、α 4、α 5、α 7、β 2和β 4的表达。所有小鼠的nAChR与谷氨酸脱羧酶（GAD）阳性的中间神经元共定位，这些中间神经元根据nAChR亚基的异质性被细分为至少四组。小鼠品系之间的一个显着差异是在CA 1亚区的星形胶质细胞亚群的nAChR的表达，其数量与nAChR免疫染色的神经元成反比。这种新的关系也与已发表的尼古丁敏感性的应变参数。试图确定菌株之间nACbR表达的这种显著差异的起源，包括比较整个nAChRalpha 4基因序列。虽然多个多态性被确定，包括两个改变nAChRalpha 4氨基酸编码，没有这些明确相关的细胞类型特异性nAChR表达的菌株相关差异。这些研究结果表明，小鼠品系特异性的行为和生理反应尼古丁可能是一个复杂的遗传因素之间的相互作用的反映，形状在哺乳动物神经系统中的这种调节性神经递质系统的表达和细胞结构的差异。(C)2003 Wiley-Liss，Inc.
The response by individuals to nicotine is likely to reflect the interaction of this compound with target nAChRs. However, resolving how different genetic backgrounds contribute to unique mouse strain-specific responses to this compound remains an important and unresolved issue. To examine this question in detail, expression of the nicotine acetylcholine receptor (nAChR) subunits alpha3, alpha4, alpha5, alpha7, beta2, and beta4 was measured in the dorsal hippocampus using immunohistochemistry in mouse strains or lines BALB/c, C3H/J, C57BL/6, CBA/J, DBA/2, Long Sleep (LS), Short Sleep (SS), and CF1. The nAChRs in all mice colocalized with glutamic acid decarboxylase (GAD)-positive interneurons that were subclassified into at least four groups based on nAChR subunit heterogeneity. A notable difference between mouse strains was the expression of nAChRs by astrocyte subpopulations in CA1 subregions whose numbers vary inversely with nAChR-immunostained neurons. This novel relationship also correlated with published parameters of strain sensitivity to nicotine. Attempts to identify the origin of this significant difference in nACbR expression among strains included comparison of the entire nAChRalpha4 gene sequence. Although multiple polymorphisms were identified, including two that changed nAChRalpha4 amino acid coding, none of these clearly correlate with strain-related differences in cell type-specific nAChR expression. These findings suggest that mouse strain-specific behavioral and physiological responses to nicotine are likely to be a reflection of a complex interplay between genetic factors that shape differences in expression and cellular architecture of this modulatory neurotransmitter system in the mammalian nervous system. (C) 2003 Wiley-Liss, Inc.