title: Developmental and degenerative modulation of GABAergic transmission in the mouse hippocampus.
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.
authors.affiliation: Departments of Veterinary Anatomy and Veterinary Toxicology, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Jinwook
authors.initials: J
authors.lastname: Kim
authors.affiliation: Departments of Veterinary Anatomy and Veterinary Toxicology, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Yeonghoon
authors.initials: Y
authors.lastname: Son
authors.affiliation: 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.
authors.forename: Juhwan
authors.initials: J
authors.lastname: Kim
authors.affiliation: Departments of Veterinary Anatomy and Veterinary Toxicology, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Sueun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Departments of Veterinary Anatomy and Veterinary Toxicology, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Sohi
authors.initials: S
authors.lastname: Kang
authors.affiliation: Departments of Veterinary Anatomy and Veterinary Toxicology, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Kyunghwan
authors.initials: K
authors.lastname: Park
authors.affiliation: Departments of Veterinary Anatomy and Veterinary Toxicology, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Departments of Veterinary Anatomy and Veterinary Toxicology, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Jong-Choon
authors.initials: JC
authors.lastname: Kim
authors.affiliation: Department of Molecular Anatomy, Faculty of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
authors.forename: Jeongtae
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Molecular Anatomy, Faculty of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
authors.forename: Chitoshi
authors.initials: C
authors.lastname: Takayama
authors.affiliation: Center for Neuroscience, Korea Institute of Science and Technology (KIST), Seoul 136-791, South Korea.
authors.forename: Heh-In
authors.initials: HI
authors.lastname: Im
authors.affiliation: Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, South Korea.
authors.forename: Miyoung
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine, Jeju National University, Jeju 690-756, South Korea. Electronic address: shint@jejunu.ac.kr.
authors.forename: Taekyun
authors.initials: T
authors.lastname: Shin
authors.affiliation: 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.
authors.forename: Changjong
authors.initials: C
authors.lastname: Moon
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects* / Q000235:genetics; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000473:pathology; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D014298:Trimethyltin Compounds / Q000633:toxicity*; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D000096922:K Cl- Cotransporters
chemical_list: D005968:Glutamate Decarboxylase; D021122:Protein Subunits; D012333:RNA, Messenger; D018079:Receptors, GABA; D027981:Symporters; D014298:Trimethyltin Compounds; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters; C492244:Viaat protein, mouse; C046488:trimethyltin
keywords: GABAergic transmission; Hippocampus; Neurodegeneration; Postnatal development; Trimethyltin