Cited by 414Nerve injury and regenerationNeuroscience and Neuropharmacology ResearchNeurogenesis and neuroplasticity mechanisms

Regulation of brain-derived neurotrophic factor and nerve growth factor mRNA in primary cultures of hippocampal neurons and astrocytes

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Zafra, F, Lindholm, D, Castren, E, Hartikka, J, Thoenen, H·1992·The Journal of Neuroscience

Abstract

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)

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Crossref · 10.1523/jneurosci.12-12-04793.1992

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Authors
Zafra, F., Lindholm, D., Castren, E., Hartikka, J., & Thoenen, H.
Affiliations
Max Planck Society (DE)
Venue
The Journal of Neuroscience
Published
1992-12-01
Volume
12
Issue
12
Pages
4793-4799
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W1597356000
Cited by
414
References
2
Citations by year
2026: 1 · 2025: 7 · 2024: 4 · 2023: 6 · 2022: 4 · 2021: 8 · 2020: 7 · 2019: 8 · 2018: 6 · 2017: 15 · 2016: 9 · 2015: 12 · 2014: 8 · 2013: 14 · 2012: 9
FWCI
8.59
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
brain-derived neurotrophic factor, nerve growth factor, mRNA regulation, hippocampal neurons, astrocytes, forskolin, adenylate cyclase, calcium ionophore, calmodulin, norepinephrine, glutamate receptors, kainic acid, nifedipine, cytokines, interleukin-1, TGF-β1, neuronal activity
MeSH terms
Cyclic AMP, Animals, Astrocytes, 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester, Calcium, Cells, Cultured, Colforsin, Glutamates, Growth Substances, Hippocampus, Isoquinolines, Kainic Acid, Kinetics, Nerve Growth Factors, Nerve Tissue Proteins, Neurons, Nifedipine, Norepinephrine, Piperazines, Potassium, RNA, Messenger, Tetradecanoylphorbol Acetate, Ionomycin, Cytokines, Quisqualic Acid, Glutamic Acid, Brain-Derived Neurotrophic Factor, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Protein Kinase Inhibitors, Rats

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