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. GABAA receptors (GABAAR) 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, ¦Â2,3 and ¦Ã2 subunits of GABAAR 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 GABAAR ¦Á2 and ¦Ã2 expression is increased especially in the vicinity of large SVZ blood vessels. GABAAR ¦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 GABAAR ¦Â2,3 receptor subunits. Within the SVZ the majority of cells have an unexpected nuclear GABAAR ¦Â2,3 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 GABAA receptors on the various cell types in the SVZ.