Developmental and degenerative modulation of GABAergictransmission in the mouse hippocampus

Abstract

-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter involved in synaptic plasticity.GABAergic transmission is also implicated in developmental and degenerative processes in the brain.The goal of the present study was to understand the developmental and degenerative regulation ofGABAergic transmission in the mouse hippocampus by examining changes in GABA receptor subunitmRNA levels and GABA-related protein expression during postnatal development of the hippocampusand trimethyltin (TMT)-induced neurodegeneration in the juvenile (postnatal day [PD] 24) and adulthippocampus (PD 56). During postnatal development, the mRNA levels of GABA A receptor (GABAAR)subunits, including 1, 4, 1, 2, and ı; GABA B receptor (GABABR) subunit 2; and the expression ofGABA-related proteins, including glutamic acid decarboxylase, vesicular GABA transporter (VGAT), andpotassium chloride cotransporter 2 increased gradually in the mouse hippocampus. The results of seizurescoring and histopathological findings in the hippocampus revealed a more pronounced response to thesame administered TMT dose in juvenile mice, compared with that in adult mice. The mRNA levels of mostGABA receptor subunits in the juvenile hippocampus, excluding GABAAR subunit 3, were dynamicallyaltered after TMT treatment. The mRNA levels of GABAAR subunits 2 and ı decreased significantly in theadult hippocampus following TMT treatment, whereas the level of GABABR subunit 1 mRNA increasedsignificantly. Among the GABA-related proteins, only VGAT decreased significantly in the juvenile andadult mouse hippocampus after TMT treatment. In conclusion, regulation of GABAergic signaling in themouse hippocampus may be related to maturation of the central nervous system and the degree of neu-rodegeneration during postnatal development and TMT-induced neurodegeneration in the experimentalanimals.