The 1, 2, 3, and 2 subunits of GABA(A) receptors show characteristic spatial and temporal expression patterns in rhombencephalic structures during normal human brain development

摘要

-Aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in adult mammalian brain, mediating its actions chiefly via a pentameric chloride ion channel, the GABA(A) receptor. Nineteen different subunits (1-6, 1-3, 1-3, , epsilon, , , 1-3) can give rise to multiple receptor subtypes that are the site of action of many clinically important drugs. In the developing brain, however, GABA(A) 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 (1, 2, 3, and 2) in the human rhombencephalon. The 2 was the most abundant subunit in all rhombencephalic structures during development and in adults, whereas subunits showed a structure- and age-characteristic distribution. The 1 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 2 gradually increased during development, showing some layer specificity in the cerebellar cortex. The 3-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 GABA(A) receptor composition. Interestingly, subunit expression in several instances differed between human and rodent brain, underlining the importance of immunohistochemical studies in humans. J. Comp. Neurol. 524:1805-1824, 2016. (c) 2015 Wiley Periodicals, Inc.