title: Cholinergic regulation of hippocampal brain-derived neurotrophic factor mRNA expression: evidence from lesion and chronic cholinergic drug treatment studies.
abstract: Quantitative in situ hybridization and northern blot analysis techniques were used to determine the effects of removal of the cholinergic input on levels and topographical distribution of brain-derived neurotrophic factor mRNA in the hippocampus of adult rats. First, the effects of partial and full fimbrial transections, which result in partial and near-total cholinergic deafferentation respectively, were compared. Twenty-one days after partial unilateral fimbrial transections, there were significant decreases in brain-derived neurotrophic factor mRNA expression throughout the hippocampal formation. Decreased expression of brain-derived neurotrophic factor mRNA was evident in all areas of localization within the hippocampal formation. The decreases amounted to 22-36% reductions compared with unlesioned control animals. Brain-derived neurotrophic factor mRNA levels were decreased to a greater extent (50-69%) following full unilateral fimbrial transections. Quantitative northern blot analysis indicated that hippocampal BDNF mRNA was decreased by 29 and 68%, three weeks after partial or full unilateral fimbrial transections, respectively. The extent of the reductions in brain-derived neurotrophic factor mRNA levels correlated with reductions in acetylcholinesterase staining density and cholinergic terminal density determined by quantitative autoradiographic analysis of [3H]vesamicol binding sites. Second, we found that chronic treatment with atropine (20 mg/kg per day for 14 days) decreased (by 54%) brain-derived neurotrophic factor mRNA levels in all areas of localization within the hippocampus. In contrast, chronic treatment with nicotine (1.18 mg/kg per day for 14 days), a treatment known to desensitize nicotinic receptors, did not affect brain-derived neurotrophic factor mRNA expression in the hippocampal formation. The findings provide evidence for cholinergic muscarinic regulation of brain-derived neurotrophic factor mRNA expression in the adult rat hippocampal formation and they suggest the existence of a tonic stimulation of brain-derived neurotrophic factor synthesis by the cholinergic afferents.
authors.affiliation: Division of Neurogerontology, Andrus Gerontology Center, University of Southern California, Los Angeles 90089-0191.
authors.forename: P A
authors.initials: PA
authors.lastname: Lapchak
authors.forename: D M
authors.initials: DM
authors.lastname: Araujo
authors.forename: F
authors.initials: F
authors.lastname: Hefti
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D000110:Acetylcholinesterase / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D009414:Nerve Growth Factors / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D009467:Neuromuscular Depolarizing Agents / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D010880:Piperidines / Q000378:metabolism; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013238:Stereotaxic Techniques
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009467:Neuromuscular Depolarizing Agents; D010880:Piperidines; D012333:RNA, Messenger; C006189:vesamicol; D009538:Nicotine; D001285:Atropine; D000110:Acetylcholinesterase; D000109:Acetylcholine