Regulation of brain-derived neurotrophic factor mRNA levels in hippocampus by neuronal activity.

Abstract:

:Neuronal activity increases synthesis of brain-derived neurotrophic factor (BDNF) mRNA in vivo and in vitro. We have investigated the pathways through which neuronal activity stimulated by kainic acid regulates BDNF mRNA levels in cultured hippocampal neurons and transgenic mice. Kainic acid induced the transcription of BDNF mRNA without influencing the mRNA stability. Interestingly, the half-life of the 4.2 kb BDNF transcript was much shorter than that of the 1.6 kb transcript (23 +/- 4 min. vs. 132 +/- 30 min). Increase in the BDNF mRNA levels by kainic acid was not blocked by the protein synthesis inhibitor cycloheximide demonstrating that BDNF is regulated as an immediate early gene in hippocampal neurons. Although calmodulin antagonists are known to abolish the effect of kainic acid on BDNF mRNA, this effect was very similar in Ca(+2)-calmodulin-dependent protein kinase II alpha knock-out mice and in wild-type mice. Surprisingly, even high doses of kainic acid failed to increase nerve growth factor (NGF) mRNA in mouse hippocampus although elevation in rat brain has been consistently observed.

journal_name

Prog Brain Res

authors

Castrén E,Berninger B,Leingärtner A,Lindholm D

doi

10.1016/s0079-6123(08)64007-8

subject

Has Abstract

pub_date

1998-01-01 00:00:00

pages

57-64

eissn

0079-6123

issn

1875-7855

pii

S0079-6123(08)64007-8

journal_volume

117

pub_type

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