Developmental and degenerative modulation of GABAergic transmission in the mouse hippocampus

Jinwook Kim; Yeonghoon Son; Juhwan Kim; Sueun Lee; Sohi Kang; Kyunghwan Park; Sung-Ho Kim; Jong-Choon Kim; Jeongtae Kim; Chitoshi Takayama; Heh-In Im; Miyoung Yang; Taekyun Shin; Changjong Moon

doi:10.1016/j.ijdevneu.2015.08.009

Developmental and degenerative modulation of GABAergic transmission in the mouse hippocampus

Int J Dev Neurosci. 2015 Dec;47(Pt B):320-32. doi: 10.1016/j.ijdevneu.2015.08.009. Epub 2015 Sep 21.

Authors

Affiliations

¹ Departments of Veterinary Anatomy and Veterinary Toxicology, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
² Departments of Veterinary Anatomy and Veterinary Toxicology, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea; Center for Neuroscience, Korea Institute of Science and Technology (KIST), Seoul 136-791, South Korea.
³ Department of Molecular Anatomy, Faculty of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
⁴ Center for Neuroscience, Korea Institute of Science and Technology (KIST), Seoul 136-791, South Korea.
⁵ Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, South Korea.
⁶ Department of Veterinary Anatomy, College of Veterinary Medicine, Jeju National University, Jeju 690-756, South Korea. Electronic address: shint@jejunu.ac.kr.
⁷ Departments of Veterinary Anatomy and Veterinary Toxicology, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea. Electronic address: moonc@chonnam.ac.kr.

PMID: 26394279
DOI: 10.1016/j.ijdevneu.2015.08.009

Abstract

γ-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 of GABAergic transmission in the mouse hippocampus by examining changes in GABA receptor subunit mRNA levels and GABA-related protein expression during postnatal development of the hippocampus and trimethyltin (TMT)-induced neurodegeneration in the juvenile (postnatal day [PD] 24) and adult hippocampus (PD 56). During postnatal development, the mRNA levels of GABA A receptor (GABAAR) subunits, including α1, α4, β1, β2, and δ; GABA B receptor (GABABR) subunit 2; and the expression of GABA-related proteins, including glutamic acid decarboxylase, vesicular GABA transporter (VGAT), and potassium chloride cotransporter 2 increased gradually in the mouse hippocampus. The results of seizure scoring and histopathological findings in the hippocampus revealed a more pronounced response to the same administered TMT dose in juvenile mice, compared with that in adult mice. The mRNA levels of most GABA receptor subunits in the juvenile hippocampus, excluding GABAAR subunit β3, were dynamically altered after TMT treatment. The mRNA levels of GABAAR subunits γ2 and δ decreased significantly in the adult hippocampus following TMT treatment, whereas the level of GABABR subunit 1 mRNA increased significantly. Among the GABA-related proteins, only VGAT decreased significantly in the juvenile and adult mouse hippocampus after TMT treatment. In conclusion, regulation of GABAergic signaling in the mouse hippocampus may be related to maturation of the central nervous system and the degree of neurodegeneration during postnatal development and TMT-induced neurodegeneration in the experimental animals.

Keywords: GABAergic transmission; Hippocampus; Neurodegeneration; Postnatal development; Trimethyltin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Analysis of Variance
Animals
Animals, Newborn
Disease Models, Animal
Gene Expression Regulation, Developmental / drug effects*
Gene Expression Regulation, Developmental / genetics
Glutamate Decarboxylase / genetics
Glutamate Decarboxylase / metabolism
Hippocampus / growth & development*
Hippocampus / metabolism*
K Cl- Cotransporters
Male
Mice
Mice, Inbred C57BL
Nerve Degeneration / chemically induced
Nerve Degeneration / metabolism*
Protein Subunits / genetics
Protein Subunits / metabolism
RNA, Messenger / metabolism
Receptors, GABA / genetics
Receptors, GABA / metabolism
Seizures / chemically induced
Seizures / pathology
Symporters / genetics
Symporters / metabolism
Trimethyltin Compounds / toxicity*
Vesicular Inhibitory Amino Acid Transport Proteins / genetics
Vesicular Inhibitory Amino Acid Transport Proteins / metabolism
gamma-Aminobutyric Acid / metabolism*

Substances

Protein Subunits
RNA, Messenger
Receptors, GABA
Symporters
Trimethyltin Compounds
Vesicular Inhibitory Amino Acid Transport Proteins
Viaat protein, mouse
trimethyltin
gamma-Aminobutyric Acid
Glutamate Decarboxylase