title: GABA(A) receptor characterization and subunit localization in the human sub-ventricular zone.
abstract: 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 γ-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 α₁, α₂, α3, β₂,₃ and γ₂ 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 α₂ and γ₂ expression is increased especially in the vicinity of large SVZ blood vessels. GABA(A)R γ₂ is the most specific to the SVZ and present on various cells that express, either glial fibrillary acidic protein (GFAPδ) 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, GFAPδ and GABA(A)R β₂,₃ receptor subunits. Within the SVZ the majority of cells have an unexpected nuclear GABA(A)R β₂,₃ 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.
authors.affiliation: Department of Anatomy with Radiology and Centre for Brain Research, Faculty of Medical and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Birger V
authors.initials: BV
authors.lastname: Dieriks
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Waldvogel
authors.forename: Hector J
authors.initials: HJ
authors.lastname: Monzo
authors.forename: Richard L M
authors.initials: RL
authors.lastname: Faull
authors.forename: Maurice A
authors.initials: MA
authors.lastname: Curtis
mesh_terms: D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D002552:Cerebral Ventricles / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058953:Neural Stem Cells / Q000737:chemistry* / Q000378:metabolism; D021122:Protein Subunits / Q000096:biosynthesis / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; D011963:Receptors, GABA-A
keywords: GABA; GABA(A) receptor; Human brain; Progenitor cell; Subventricular zone