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Neonatal lesions of the ventral hippocampal formation alter GABA-A receptor subunit mRNA expression in adult rat frontal pole.

Abstract：

BACKGROUND:Gamma-aminobutyric acid (GABA)-ergic function is altered in schizophrenia. Of particular interest is the altered central nervous system expression of GABA-A receptor subunits, as changes in subunit expression account for recognized differences in mammalian brain function making them inviting targets for novel psychotropic agents. Excitotoxic neonatal lesions of the ventral hippocampal formation (NVHL) in rats reproduce numerous aspects of schizophrenia, including decreased mRNA expression of the GABA synthesizing enzyme glutamic acid decarboxylase-67, though their impact on subunit expression is unknown. METHODS:We utilized quantitative reverse transcription polymerase chain reaction to investigate mRNA expression of the alpha1, alpha5, and gamma2s GABA-A receptor subunits in the frontal pole of water-deprived adult NVHL and SHAM-lesioned animals. RESULTS:Messenger RNA expression for all three GABA-A subunits (alpha1-NVHL: 18.5 +/- 1.6 pg/mug total pooled RNA, SHAM: 11.3 +/- .4; alpha5-NVHL: 5.1 +/- .6; SHAM: 3.5 +/- .7; and gamma2s-NVHL: 10.8 +/- 1.7; SHAM: 7.2 +/- 1.5) was higher in NVHL, though only levels of alpha1 differed significantly after correction for multiple comparisons. Levels of a control mRNA, neuronal specific enolase, were similar in the two groups. CONCLUSIONS:These data indicate that NVHL reproduce changes in cortical GABA-A receptor subunit expression seen in schizophrenia, suggesting this animal model may facilitate efforts to clarify the physiologic significance of altered GABA function and to develop novel targets for therapeutic interventions.

journal_name

Biol Psychiatry

journal_title

Biological psychiatry

authors

Mitchell CP,Grayson DR,Goldman MB

doi

10.1016/j.biopsych.2004.09.017

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

49-55

issue

1

eissn

0006-3223

issn

1873-2402

pii

S0006-3223(04)01004-2

journal_volume

57

pub_type

杂志文章

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