PMID- 1281495 OWN - NLM STAT- MEDLINE DCOM- 19930115 LR - 20211025 IS - 0270-6474 (Print) IS - 1529-2401 (Electronic) IS - 0270-6474 (Linking) VI - 12 IP - 12 DP - 1992 Dec TI - Regulation of brain-derived neurotrophic factor and nerve growth factor mRNA in primary cultures of hippocampal neurons and astrocytes. PG - 4793-9 AB - Brain-derived neurotrophic factor (BDNF) and NGF are both expressed by neurons in the hippocampus. In previous studies, it has been demonstrated that both BDNF and NGF mRNA levels are regulated by neuronal activity. Upregulation is predominantly regulated by the glutamate (NMDA and non-NMDA receptors); downregulation, predominantly by the GABA system (Zafra et al., 1990, 1991). In neuronal cultures of the rat hippocampus, potassium depolarization and kainic acid-mediated increases in BDNF and NGF mRNA were eliminated in a dose-dependent manner by the calcium channel blocker nifedipine. Conversely, calcium ionophores (Bay-K8644 and ionomycin) augmented BDNF and NGF mRNA levels by a calmodulin-mediated mechanism. In view of the fact that many potential modulators (conventional transmitters and neuropeptides) of neuronal and astrocytic BDNF and NGF mRNA synthesis may act via the adenylate cyclase system, we studied the effect of forskolin, an activator of adenylate cyclase. Indeed, forskolin enhanced the effects of calcium ionophores and kainic acid on BDNF and NGF mRNA levels. Cytokines, such as interleukin-1 and transforming growth factor-beta 1, which have previously been shown to increase NGF mRNA markedly in astrocytes, were without effect on neuronal BDNF and NGF mRNA levels. In contrast to neuronal cultures, where the regulation of BDNF and NGF mRNA was generally very similar, the regulation in astrocytes was distinctly different. All the cytokines that produce a marked increase in NGF mRNA were without effect on astrocyte BDNF mRNA levels, which under basic conditions were below the detection limit. However, norepinephrine produced a marked elevation of BDNF mRNA in astrocytes, an effect that was further enhanced by glutamate receptor agonists.(ABSTRACT TRUNCATED AT 250 WORDS) FAU - Zafra, F AU - Zafra F AD - Department of Neurochemistry, Max Planck Institute for Psychiatry, Planegg-Martinsried, Germany. FAU - Lindholm, D AU - Lindholm D FAU - Castren, E AU - Castren E FAU - Hartikka, J AU - Hartikka J FAU - Thoenen, H AU - Thoenen H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cytokines) RN - 0 (Glutamates) RN - 0 (Growth Substances) RN - 0 (Isoquinolines) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Piperazines) RN - 0 (Protein Kinase Inhibitors) RN - 0 (RNA, Messenger) RN - 1F7A44V6OU (Colforsin) RN - 3KX376GY7L (Glutamic Acid) RN - 56092-81-0 (Ionomycin) RN - 71145-03-4 (3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester) RN - 84477-87-2 (1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine) RN - 8OC22C1B99 (Quisqualic Acid) RN - E0399OZS9N (Cyclic AMP) RN - I9ZF7L6G2L (Nifedipine) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) RN - RWP5GA015D (Potassium) RN - SIV03811UC (Kainic Acid) RN - SY7Q814VUP (Calcium) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine MH - 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/pharmacology MH - Animals MH - Astrocytes/drug effects/*metabolism MH - Brain-Derived Neurotrophic Factor MH - Calcium/metabolism/pharmacology MH - Cells, Cultured MH - Colforsin/pharmacology MH - Cyclic AMP/metabolism MH - Cytokines/*pharmacology MH - Glutamates/pharmacology MH - Glutamic Acid MH - Growth Substances/*pharmacology MH - Hippocampus/*metabolism MH - Ionomycin/pharmacology MH - Isoquinolines/pharmacology MH - Kainic Acid/pharmacology MH - Kinetics MH - Nerve Growth Factors/*biosynthesis/genetics MH - Nerve Tissue Proteins/*biosynthesis/genetics MH - Neurons/drug effects/*metabolism MH - Nifedipine/pharmacology MH - Norepinephrine/pharmacology MH - Piperazines/pharmacology MH - Potassium/pharmacology MH - Protein Kinase Inhibitors MH - Quisqualic Acid/pharmacology MH - RNA, Messenger/isolation & purification/*metabolism MH - Rats MH - Tetradecanoylphorbol Acetate/pharmacology PMC - PMC6575775 EDAT- 1992/12/01 00:00 MHDA- 1992/12/01 00:01 PMCR- 1993/06/01 CRDT- 1992/12/01 00:00 PHST- 1992/12/01 00:00 [pubmed] PHST- 1992/12/01 00:01 [medline] PHST- 1992/12/01 00:00 [entrez] PHST- 1993/06/01 00:00 [pmc-release] AID - 10.1523/JNEUROSCI.12-12-04793.1992 [doi] PST - ppublish SO - J Neurosci. 1992 Dec;12(12):4793-9. doi: 10.1523/JNEUROSCI.12-12-04793.1992.