Brain-derived neurotrophic factor increases neurotrophin-3 expression in cerebellar granule neurons.
Neurotrophin-3 (NT-3) is a member of the neurotrophin gene family and is highly expressed in the developing rat cerebellum. Here we show that brain-derived neurotrophic factor (BDNF) increased by approximately 10-fold the NT-3 mRNA levels in cultured cerebellar granule neurons isolated from postnatal rats, whereas nerve growth factor (NGF) and NT-3 itself had no effect. The effect of BDNF was additive to that of triiodothyronine (T3), which also increased NT-3 mRNA in these neurons. The drug K252a inhibited the BDNF-mediated stimulation of NT-3 expression, suggesting an involvement of trkB receptors. Nuclear run-on experiments showed that BDNF enhanced NT-3 transcription, whereas the stability of NT-3 mRNA remained unchanged. The data presented are the first demonstration that one neurotrophin regulates the expression of another and provide evidence that NT-3 production in granule neurons is regulated by both BDNF and T3.
Leingärtner
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A
Department of Neurochemistry, Max Planck Institute for Psychiatry, Martinsried, Germany.
Heisenberg
C P
CP
Kolbeck
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R
Thoenen
H
H
Lindholm
D
D
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D002531:Cerebellum / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D020933:Neurotrophin 3; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects; D014284:Triiodothyronine / Q000494:pharmacology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D012333:RNA, Messenger; D014284:Triiodothyronine