PMID- 10101239 OWN - NLM STAT- MEDLINE DCOM- 19990521 LR - 20190826 IS - 0169-328X (Print) IS - 0169-328X (Linking) VI - 67 IP - 1 DP - 1999 Apr 6 TI - Hippocampal neurotrophin and trk receptor mRNA levels are altered by local administration of nicotine, carbachol and pilocarpine. PG - 124-36 AB - Cholinergic receptor agonists nicotine (nicotinic), carbachol (nicotinic/muscarinic) and pilocarpine (muscarinic) were administered into the hippocampus and mRNA levels of neurotrophins and their receptors determined using in situ hybridisation. Drug doses were carefully chosen to avoid the potentially confounding effects of seizure and cell death. Nicotine caused a long-lasting increase in nerve growth factor (NGF) mRNA in all subfields of the hippocampus. The increase was evident from 24 h up to 72 h after drug administration. This increase was dependent on excitatory amino acid neurotransmission as it was blocked by administration of an AMPA or NMDA receptor antagonist. In contrast, carbachol and pilocarpine produced a transient increase in NGF mRNA levels present 4-8 h after drug administration. Pilocarpine caused a transient increase in hippocampal brain-derived neurotrophic factor (BDNF) levels, with carbachol and nicotine showing the same trend. Nicotine and carbachol caused transient decreases in NT-3 mRNA levels in dentate gyrus and CA2 with pilocarpine showing a similar trend. Increases in mRNA encoding full-length trkB were seen 8 h after nicotine, with nicotine also causing elevations in a mRNA encoding a truncated isoform (trkB.T2). TrkC mRNA was not altered by any of the conditions used. The study suggests that muscarinic and nicotinic receptor activation in the hippocampus causes transient changes in all of the neurotrophins, but that NGF levels are selectively up-regulated by nicotinic receptor stimulation. The reciprocal interaction between NGF and ascending cholinergic systems may be a component of the cognitive enhancing effects of nicotine. CI - Copyright 1999 Elsevier Science B.V. FAU - French, S J AU - French SJ AD - Biochemical Neuropharmacology Group, Neuroscience Research Centre and Division of Biochemistry and Molecular Biology, GKT School of Biomedical Sciences, Guy's Hospital Campus, London SE1 9RT, UK. FAU - Humby, T AU - Humby T FAU - Horner, C H AU - Horner CH FAU - Sofroniew, M V AU - Sofroniew MV FAU - Rattray, M AU - Rattray M LA - eng GR - Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Brain Res Mol Brain Res JT - Brain research. Molecular brain research JID - 8908640 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cholinergic Agonists) RN - 0 (Muscarinic Agonists) RN - 0 (Nerve Growth Factors) RN - 0 (Neuroprotective Agents) RN - 0 (Neurotrophin 3) RN - 0 (Nicotinic Agonists) RN - 0 (Proto-Oncogene Proteins) RN - 0 (RNA, Messenger) RN - 0 (Receptor, Ciliary Neurotrophic Factor) RN - 0 (Receptor, Nerve Growth Factor) RN - 0 (Receptors, Nerve Growth Factor) RN - 01MI4Q9DI3 (Pilocarpine) RN - 3KX376GY7L (Glutamic Acid) RN - 6M3C89ZY6R (Nicotine) RN - 8Y164V895Y (Carbachol) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, trkA) RN - EC 2.7.10.1 (Receptor, trkC) RN - N9YNS0M02X (Acetylcholine) SB - IM MH - Acetylcholine/physiology MH - Animals MH - Behavior, Animal/physiology MH - Brain Chemistry/drug effects/physiology MH - Brain-Derived Neurotrophic Factor/genetics MH - Carbachol/*pharmacology MH - Cell Death/drug effects MH - Cholinergic Agonists/pharmacology MH - Cholinergic Fibers/chemistry/physiology MH - Epilepsy/chemically induced/physiopathology MH - Gene Expression/drug effects/physiology MH - Glutamic Acid/metabolism MH - Hippocampus/chemistry/physiology MH - In Situ Hybridization MH - Male MH - Muscarinic Agonists/*pharmacology MH - Nerve Growth Factors/*genetics MH - Neuroprotective Agents/metabolism MH - Neurotrophin 3 MH - Nicotine/*pharmacology MH - Nicotinic Agonists/*pharmacology MH - Pilocarpine/*pharmacology MH - Proto-Oncogene Proteins/*genetics MH - RNA, Messenger/analysis MH - Rats MH - Rats, Sprague-Dawley MH - Receptor Protein-Tyrosine Kinases/*genetics MH - Receptor, Ciliary Neurotrophic Factor MH - Receptor, Nerve Growth Factor MH - Receptor, trkA MH - Receptor, trkC MH - Receptors, Nerve Growth Factor/*genetics MH - Septal Nuclei/chemistry/cytology/physiology MH - Synaptic Transmission/physiology EDAT- 1999/04/02 00:00 MHDA- 1999/04/02 00:01 CRDT- 1999/04/02 00:00 PHST- 1999/04/02 00:00 [pubmed] PHST- 1999/04/02 00:01 [medline] PHST- 1999/04/02 00:00 [entrez] AID - S0169328X99000480 [pii] AID - 10.1016/s0169-328x(99)00048-0 [doi] PST - ppublish SO - Brain Res Mol Brain Res. 1999 Apr 6;67(1):124-36. doi: 10.1016/s0169-328x(99)00048-0.