Neurotrophins regulate gene expression (mentions NT-3)

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(Mentions NT-3)

Abstract from Eur J Neurosci. 2004 Aug;20(3):701-8.

Neurotrophins induce short-term and long-term changes of cortical

neurotrophin expression.

Patz S, Wahle P.

AG Entwicklungsneurobiologie, Fakultat fur Biologie, ND 6/72,

Ruhr-Universitaet, 44780 Bochum, Germany.

Neuronal activity, hormones, transmitters, physical exercise and

enrichment influence cortical neurotrophin expression. Neurotrophins

then elicit structural and physiological changes, and regulate gene

expression. This prompted the hypothesis that neurotrophins themselves

are involved in regulating neurotrophin expression. Here we investigated

the mRNA expression level of brain-derived neurotrophic factor (BDNF),

neurotrophin-4 (NT-4), NT-3 and nerve growth factor (NGF) as well as the

tyrosine receptor kinases TrkB and TrkC receptor in response to BDNF,

NT-4, NT-3 and NGF pulses in organotypic cortex cultures. Single

neurotrophin pulses evoked a dramatic up- or down-regulation of some,

but not all four, neurotrophin mRNAs, even within 3-24 h, indicating an

immediate impact on neurotrophin transcription. Most strikingly,

neurotrophin pulses during the first 10 days in vitro (DIV) potentiated

the expression of some neurotrophin mRNAs at 20 DIV, suggesting that

early trophic factor experience influences the expression levels seen

later in development. The NT-3 mRNA expression, for example, was

consistently promoted by NGF and BDNF, suggesting that these two factors

help to maintain the low level of NT-3 found in adult cortex. Rapid

bidirectional changes characterized the NT-4 mRNA expression. A single

pulse of NT-4 transiently increased NT-4 mRNA, whereas a BDNF pulse

transiently reduced NT-4 mRNA. Surprisingly, NGF strongly potentiated

BDNF mRNA and in particular NT-4 mRNA. By contrast, TrkB mRNA remained

constant at ages or time points at which other mRNAs amplified from the

very same cDNA libraries revealed dramatic increases or decreases. Our

study suggests the existence of a complex regulatory neurotrophin

network controlling the expression of other neurotrophins.