title: The α1, α2, α3, and γ2 subunits of GABAA receptors show characteristic spatial and temporal expression patterns in rhombencephalic structures during normal human brain development.
abstract: γ-Aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in adult mammalian brain, mediating its actions chiefly via a pentameric chloride ion channel, the GABAA receptor. Nineteen different subunits (α1-6, β1-3, γ1-3, δ, ε, π, θ, ρ1-3) can give rise to multiple receptor subtypes that are the site of action of many clinically important drugs. In the developing brain, however, GABAA receptors mediate excitatory actions due to an increased chloride concentration within neurons and seem to control cell proliferation, migration, differentiation, synapse maturation, and cell death. Little is known about the distribution of single subunits in the human brain. Here we describe developmental changes in the immunohistochemical distribution of four subunits (α1, α2, α3, and γ2) in the human rhombencephalon. The γ2 was the most abundant subunit in all rhombencephalic structures during development and in adults, whereas α subunits showed a structure- and age-characteristic distribution. The α1 was expressed prenatally in the molecular and Purkinje cell layer, but only postnatally in the granule cell layer and the dentate nucleus. Expression was completely absent in the inferior olivary nucleus. The α2 gradually increased during development, showing some layer specificity in the cerebellar cortex. The α3-immunoreactivity in the cerebellar cortex was relatively weak, but it was abundantly observed in different cell populations in the subcortical cerebellar structures. Structure- and age-characteristic colocalization between subunits during development suggests differences in GABAA receptor composition. Interestingly, subunit expression in several instances differed between human and rodent brain, underlining the importance of immunohistochemical studies in humans.
authors.affiliation: Institute of Neurology, Neurodegeneration Research Group, Medical University of Vienna, Vienna, Austria.
authors.forename: Tamara
authors.initials: T
authors.lastname: Stojanovic
authors.affiliation: Department of Histology and Embryology, Medical Faculty, Vojvodina, Serbia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Capo
authors.affiliation: Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, The Netherlands; SEIN - Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands; Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, The Netherlands.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
authors.affiliation: Inserm U1141, Paris, France; Univ. Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France, Department of Pathology, Lariboisière Hospital, APHP, Paris, France.
authors.forename: Homa
authors.initials: H
authors.lastname: Adle-Biassette
authors.affiliation: Division of Laboratory Animal Science and Genetics, Medical University of Vienna, Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Höger
authors.affiliation: Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Sieghart
authors.affiliation: Institute of Neurology, Neurodegeneration Research Group, Medical University of Vienna, Vienna, Austria.
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Kovacs
authors.affiliation: Institute of Neurology, Neurodegeneration Research Group, Medical University of Vienna, Vienna, Austria.|Department of Neurology, Medical University of Vienna, Vienna, Austria.
authors.forename: Ivan
authors.initials: I
authors.lastname: Milenkovic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D005260:Female; D005333:Fetus; D058785:GABA-A Receptor Agonists / Q000145:classification / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D021122:Protein Subunits / Q000378:metabolism
chemical_list: D058785:GABA-A Receptor Agonists; D021122:Protein Subunits
keywords: AB_2108828; AB_221544; AB_2340281; AB_2532077; GABAA receptor; cerebellum; human brain development; rhombencephalon