Details

Autor(en) / Beteiligte

• Berninger, B
• Marty, S
• Zafra, F
• da Penha Berzaghi, M
• Thoenen, H
• Lindholm, D

Titel

GABAergic stimulation switches from enhancing to repressing BDNF expression in rat hippocampal neurons during maturation in vitro

Ist Teil von

• Development (Cambridge), 1995-08, Vol.121 (8), p.2327-2335

Ort / Verlag

England: The Company of Biologists Limited

Erscheinungsjahr

1995

Quelle

MEDLINE

Beschreibungen/Notizen

• gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the adult mammalian central nervous system. However, GABA depolarizes immature rat hippocampal neurons and increases intracellular Ca2+ ([Ca2+]i). Here we show, that GABA and the GABAA receptor agonist muscimol induce c-Fos immunoreactivity and increase BDNF mRNA expression in embryonic hippocampal neurons cultured for 5 days. In contrast, after 3 weeks in culture, GABA and muscimol failed to induce c-fos and BDNF expression. Fura-2 fluorescence microscopy revealed that muscimol produces a dihydropyridine-sensitive transient increase in [Ca2+]i, comparable to the effect of the non-NMDA receptor agonist kainic acid in neurons cultured for 5 days, but not in 3-week-old cultures. The increase in c-Fos immunoreactivity and BDNF mRNA levels by GABA were dependent upon the activation of voltage-gated Ca2+ channels, as shown using the L-type specific Ca2+ channel blocker nifedipine. The differential regulation of c-fos and BDNF expression by GABA and muscimol in developing and mature hippocampal neurons is due to a switch in the ability of GABAA receptors to activate voltage-gated Ca2+ channels. These observations support the hypothesis that GABA might have neurotrophic effects on embryonic or perinatal hippocampal neurons, which are mediated by BDNF.