GABA_A receptor characterization and subunit localization in the human sub ventricular zone

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• 作者：Birger V. Dieriks ; Henry J. Waldvogel ; Hector J. Monzo ; Richard L.M. Faull ; Maurice A. Curtis
• 关键词：GABA ; GABAA receptor ; Subventricular zone ; Human brain ; Progenitor cell
• 刊名：Journal of Chemical Neuroanatomy
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：52
• 期：Complete
• 页码：58-68
• 全文大小：4207 K

文摘

It is now well established that the human brain continuously produces new stem cells until well into old age. One of these stem-cell rich areas in the human brain is the sub-ventricular zone (SVZ). The human SVZ is organized in four distinctive layers containing type A, B and C cells. To date, no studies have investigated the distribution of inhibitory neurotransmitters such as ¦Ã-aminobutyric acid (GABA) and their respective receptors on the different cell types in the human SVZ. GABA_A receptors (GABA_AR) are ubiquitously expressed, inhibitory heteropentameric chloride ion channels comprised of a variety of subunits that are targeted by many prescribed drugs. In this study we present detailed immunohistochemical data on the regional and cellular localization of ¦Á₁, ¦Á₂, ¦Á₃, ¦Â_2,3 and ¦Ã₂ subunits of GABA_AR in the human SVZ. The results from our double and triple labeling studies demonstrate that the cell types and subunit composition throughout the SVZ is heterogeneous; the thickness of the SVZ and GABA_AR ¦Á₂ and ¦Ã₂ expression is increased especially in the vicinity of large SVZ blood vessels. GABA_AR ¦Ã₂ is the most specific to the SVZ and present on various cells that express, either glial fibrillary acidic protein (GFAP¦Ä) or polysialic acid-neural cell adhesion molecule (PSA-NCAM) separately, or together in a respective ratio of 7:6:2. Proliferating (type C) cells in the SVZ express GAD65/67, GFAP¦Ä and GABA_AR ¦Â_2,3 receptor subunits. Within the SVZ the majority of cells have an unexpected nuclear GABA_AR ¦Â_2,3 expression that is inversely proportional to that of PCNA (proliferating cell nuclear antigen marker), which is a very different pattern of expression compared with underlying caudate nucleus cells. Taken together our results provide a detailed description of the chemo-architecture of the adult human SVZ demonstrating the importance of GABA and GABA_A receptors on the various cell types in the SVZ.