title: Ibotenic acid lesion of nucleus basalis magnocellularis differentially affects cholinergic, glutamatergic and GABAergic markers in cortical rat brain regions.
abstract: The present study was undertaken to study the effect of reduced cortical cholinergic activity on gamma-aminobutyric acid (GABA)ergic and glutamatergic mechanisms in cholinoceptive cortical target regions which are assumed to play an important role for realizing cognitive functions. The densities of cortical muscarinic cholinergic receptor subtypes and corresponding receptor genes m1 through m4, N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) and kainate glutamate receptor subtypes as well as GABAA and benzodiazepine receptors were measured in rats 1 week after unilateral ibotenic acid lesion of the nucleus basalis magnocellularis (Nbm) applying quantitative receptor autoradiography and in situ hybridization. Ibotenic acid lesion resulted in a striking loss of acetylcholinesterase (AChE) staining in the lesioned Nbm which is associated with a 60% decrease in AChE staining and a 30% reduction in [3H]hemicholinium-3 binding in frontal and parietal cortical regions as well fore- and hindlimb areas ipsilateral to the lesion, being more prominent in the more rostral cortical regions. M1-muscarinic cholinergic receptor binding was not changed in any of the cortical regions studied 1 week after lesion. M2-muscarinic receptor binding levels are slightly increased in the parietal cortex only. The lesion-induced increase in parietal cortical M2-muscarinic receptor binding is complemented by an increase in the hybridization signal for the corresponding m4-mRNA transcript. In cortical regions displaying a reduced activity of AChE and decreased levels of high-affinity choline uptake sites due to forebrain cholinergic lesion, NMDA receptor binding was markedly reduced in comparison to the unlesioned brain side whereas AMPA and kainate binding has been significantly increased in these regions. Muscimol binding to GABAA receptors was increased in the rostral portions of frontal and parietal cortices as compared with the unlesioned brain side. Binding levels of benzodiazepine receptors were not affected by the lesion in any of the cortical regions studied. The differential changes in glutamate and GABA receptor subtypes following lesion might be regarded as the consequence of a cortical reorganization compensating for the reduced cholinergic presynaptic input. The data further suggest that presynaptic cortical cholinergic deficits might affect both glutamatergic and GABAergic functions with different intensity and different directions.
authors.affiliation: Paul Flechsig Institute for Brain Research, Department of Neurochemistry, University of Leipzig, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Rossner
authors.forename: R
authors.initials: R
authors.lastname: Schliebs
authors.forename: V
authors.initials: V
authors.lastname: Bigl
mesh_terms: D000109:Acetylcholine / Q000172:deficiency*; D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002540:Cerebral Cortex / Q000737:chemistry* / Q000187:drug effects / Q000503:physiopathology; D005445:Flunitrazepam; D018698:Glutamic Acid / Q000502:physiology; D006426:Hemicholinium 3; D007051:Ibotenic Acid; D017403:In Situ Hybridization; D008297:Male; D009118:Muscimol; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000032:analysis* / Q000235:genetics; D011963:Receptors, GABA-A / Q000032:analysis* / Q000235:genetics; D018092:Kainic Acid Receptors / Q000032:analysis* / Q000235:genetics; D011976:Receptors, Muscarinic / Q000032:analysis* / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis* / Q000235:genetics; D013377:Substantia Innominata / Q000737:chemistry* / Q000187:drug effects / Q000503:physiopathology
chemical_list: D000109:Acetylcholine; D000110:Acetylcholinesterase; D015415:Biomarkers; D005445:Flunitrazepam; D018698:Glutamic Acid; D006426:Hemicholinium 3; D007051:Ibotenic Acid; D009118:Muscimol; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D018092:Kainic Acid Receptors; D011976:Receptors, Muscarinic; D016194:Receptors, N-Methyl-D-Aspartate