Neonatal lesions of the ventral hippocampal formation alter GABA-A receptor subunit mRNA expression in adult rat frontal pole.
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.
Mitchell
Colin P
CP
Psychiatric Institute, University of Illinois at Chicago in affiliation with University of Chicago, 1601 W. Taylor, Chicago, IL 60612, USA.
Grayson
Dennis R
DR
Goldman
Morris B
MB
D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D001927:Brain Diseases / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000293:injuries* / Q000473:pathology / Q000502:physiology; D008297:Male; D011247:Pregnancy; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D021122:Protein Subunits; D012333:RNA, Messenger; D011963:Receptors, GABA-A