Cholinergic regulation of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) but not neurotrophin-3 (NT-3) mRNA levels in the developing rat hippocampus.
In previous experiments it has been demonstrated that the synthesis of BDNF (brain-derived neurotrophic factor) and NGF in neurons of the hippocampus is regulated by neuronal activity. The glutamate system is predominantly responsible for upregulation and the GABAergic system for downregulation both in vitro and in vivo (Zafra et al., 1990, 1991). The aim of the present study is to examine the extent to which the cholinergic system is also involved in the regulation of NGF and BDNF mRNA and whether the regulatory contribution of the cholinergic system changes during development. Partial transection of the fimbria fornix bundle in the second postnatal week resulted in a reduction of BDNF and NGF mRNA levels in the hippocampus, suggesting that septal cholinergic input is involved in the regulation of hippocampal BDNF and NGF mRNA levels. Because the fimbria fornix bundle also contains fibers other than cholinergic ones, we further evaluated the importance of the cholinergic influence by injecting pilocarpine, a muscarinic agonist. Pilocarpine markedly increased hippocampal BDNF and NGF mRNA levels in both early postnatal and adult rats. In situ hybridization experiments demonstrated that pilocarpine led to an increase in BDNF expression in the CA1-CA4 regions of the hippocampus and in the dentate gyrus. However, pilocarpine increased NGF mRNA only in those neurons of the dentate gyrus and CA1-CA4 regions that also expressed NGF mRNA in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
da Penha Berzaghi
M
M
Department of Neurochemistry, Max Planck Institute for Psychiatry, Planegg Martinsried, Germany.
Cooper
J
J
Castrén
E
E
Zafra
F
F
Sofroniew
M
M
Thoenen
H
H
Lindholm
D
D
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D017403:In Situ Hybridization; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D020933:Neurotrophin 3; D010862:Pilocarpine / Q000494:pharmacology*; D011712:Pyramidal Tracts / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D015347:RNA Probes; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D015347:RNA Probes; D012333:RNA, Messenger; D010862:Pilocarpine; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D012601:Scopolamine; D007608:Kainic Acid