title: Differential expression of immediate early genes in distinct layers of rat cerebral cortex after selective immunolesion of the forebrain cholinergic system.
abstract: The aim of this study was to show whether reduction or loss of cortical cholinergic activity results in any particular change in the expression of the proto-oncogenes c-fos and/or c-jun. To produce cortical cholinergic hypofunction, the monoclonal antibody, 192IgG, to the low-affinity nerve growth factor receptor p75NGFR coupled to a cytotoxin, saporin, was used as an efficient and selective immunotoxin for cholinergic neurons in rat basal forebrain. Brain sections of adult rats that had received an intracerebroventricular injection of 4 micrograms of the 192IgG-saporin were subjected to in situ hybridization using oligonucleotides to detect c-fos and c-jun mRNA. Autoradiographs obtained were evaluated by quantitative image analysis. Seven days following injection of the immunotoxin there was a dramatic loss in acetylcholinesterase staining in frontal, parietal, piriform, temporal, and occipital cortices, hippocampus, and olfactory bulb, but not in the striatum and cerebellum. In situ hybridization revealed a considerable increase in the level of c-fos mRNA in the lateral septum following the cholinergic lesion, whereas in the medial septum both c-fos and c-jun mRNA were elevated. Immunolesioning led to a distinct and specific increase in the level of c-jun but not c-fos mRNA in the parietal and occipital cortex that was restricted to cortical layer IV. These data suggest that reduced cortical cholinergic activity differentially regulates expression of c-fos/c-jun genes in distinct cortical regions of the rat brain.
authors.affiliation: Paul Flechsig Institute for Brain Research, Department of Neurochemistry, University of Leipzig, Medical Faculty, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Rossner
authors.forename: J R
authors.initials: JR
authors.lastname: Perez-Polo
authors.forename: R G
authors.initials: RG
authors.lastname: Wiley
authors.forename: R
authors.initials: R
authors.lastname: Schliebs
authors.forename: V
authors.initials: V
authors.lastname: Bigl
mesh_terms: D000110:Acetylcholinesterase / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal; D001345:Autoradiography; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology*; D017781:Genes, Immediate-Early / Q000235:genetics*; D000922:Immunotoxins / Q000633:toxicity; D008297:Male; D010275:Parasympathetic Nervous System / Q000276:immunology / Q000502:physiology*; D016548:Prosencephalon / Q000276:immunology / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D000110:Acetylcholinesterase