GABAA receptor subtype changes in the substantia nigra of the rat following quinolinate lesions in the striatum: a correlative in situ hybridization and immunohistochemical study.
This study investigates the pattern of distribution of GABAA receptor subunit subtypes in the substantia nigra of the rat using in situ hybridization techniques and immunohistochemistry at the light microscopic level following unilateral quinolinate lesions in the striatum. The main purpose of this study was to first identify the variety and regional distribution of GABAA receptor subtype messenger RNAs in the normal substantia nigra and, second, to determine if this pattern and level of expression of GABAA receptor subtypes in the substantia nigra is affected following quinolinate-induced degeneration of the GABAergic striatonigral projection neurons. The study is based on a comparison of adjacent sections using: (i) in situ hybridization and oligonucleotide probes selective for 13 of the GABAA receptor subunits; and (ii) immunohistochemistry and antibodies specific to three protein subunits of the GABAA receptor complex. The results show that the GABAA receptor in the normal substantia nigra pars reticulata has a molecular configuration comprising of the alpha 1, beta 2, and gamma 2 subtypes and that following quinolinate lesions of the striatum the subtype configuration of the GABAA receptors remains unaltered, but that there is a marked increase in the level of expression of the alpha 1, beta 2 and gamma 2 subtypes. In confirmation of these findings, the immunohistochemical results show increased immunoreactivity for the alpha 1, beta 2,3 and gamma 2 GABAA receptor subtypes in the substantia nigra following degeneration of GABAergic striatonigral neurons. The details of these findings are discussed with reference to previous studies and with regard to the implications that these results may have for specific GABAergic neurodegenerative diseases of the human basal ganglia, such as Huntington's disease.
Nicholson
L F
LF
Department of Anatomy, School of Medicine, University of Auckland, New Zealand.
Waldvogel
H J
HJ
Faull
R L
RL
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017378:Quinolinic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism*
D011963:Receptors, GABA-A; D017378:Quinolinic Acid