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

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 gamma-aminobutyric acid (GABA) and their respective receptors on the different cell types in the human SVZ. GABA(A) receptors (GABA(A)R) 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 alpha(1), alpha(2), alpha(3), beta(2,3) and gamma(2) subunits of GABA(A)R 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(A)R alpha(2) and gamma(2) expression is increased especially in the vicinity of large SVZ blood vessels. GABA(A)R gamma(2) is the most specific to the SVZ and present on various cells that express, either glial fibrillary acidic protein (GFAP delta) 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 delta and GABA(A)R beta(2,3) receptor subunits. Within the SVZ the majority of cells have an unexpected nuclear GABA(A)R beta(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. (C) 2013 Elsevier B.V. All rights reserved.