Depolarizing Stimuli Regulate Nerve Growth Factor Gene Expression in Cultured Hippocampal Neurons

Although trophic factors and neuronal activity have been implicated in regulating functional synaptic circuits, the relationship of trophic interaction to impulse activity in synaptogenesis remains unclear. Using cultured hippocampus as a model system, we provide direct evidence that depolarization...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1991-07, Vol.88 (14), p.6289-6292
Main Authors: Lu, Bai, Yokoyama, Midori, Dreyfus, Cheryl F., Black, Ira B.
Format: Article
Language:English
Subjects:
Animals
Behavioral neuroscience
Biological and medical sciences
Cell physiology
Cells, Cultured
Cultured cells
Depolarization
Electric Stimulation
Embryo, Mammalian
Fundamental and applied biological sciences. Psychology
Gene expression
Gene Expression - drug effects
Gene expression regulation
Gene Expression Regulation - drug effects
Gene Expression Regulation - physiology
Hippocampus - physiology
Kinetics
Membrane Potentials - drug effects
Messenger RNA
Molecular and cellular biology
Nerve Growth Factors - genetics
Nerves
Neurons
Neurons - drug effects
Neurons - physiology
Neurotransmission
Organ Culture Techniques
Picrotoxin - pharmacology
Potassium
Potassium - pharmacology
Rats
Rats, Inbred Strains
RNA
RNA - isolation & purification
RNA, Messenger - analysis
RNA, Messenger - genetics
Tetrodotoxin - pharmacology
Veratridine - pharmacology
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Summary:Although trophic factors and neuronal activity have been implicated in regulating functional synaptic circuits, the relationship of trophic interaction to impulse activity in synaptogenesis remains unclear. Using cultured hippocampus as a model system, we provide direct evidence that depolarization and impulse activity specifically increase nerve growth factor gene expression in neurons. Depolarizing stimuli, such as a high K+concentration or the Na+channel agonist veratridine, elicited a 3-fold increase of nerve growth factor mRNA levels in both explant and dissociated cultures. Blockade of depolarization by tetrodotoxin prevented the increase of neuronal nerve growth factor mRNA. Further, nerve growth factor gene expression was stimulated by picrotoxin, a γ-aminobutyric acid antagonist frequently used to enhance hippocampal neuronal activity. Impulse regulation of trophic gene function may be relevant to developmental synaptogenesis and synaptic strengthening in learning and memory.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.88.14.6289