NT-3 modulates BDNF and proBDNF levels in naïve and kindled rat hippocampus.
Both mature and precursor forms of neurotrophins regulate nerve development, survival and plasticity. Brain-derived neurotrophic factor (BDNF) synthesis and secretion in turn are regulated by neuronal activity, such as epilepsy. Further, neurotrophins themselves are regulated by neurotrophin levels. Neurotrophin-3 (NT-3) and BDNF in particular can be co-expressed and each can regulate the levels of the other. This regulation is thought to be mediated through receptor tyrosine kinase (Trk) activity. It is not known whether this neurotrophin-neurotrophin interaction occurs in hippocampal tissue in vivo, or how it is influenced by neuronal activation. In this study, we explored the reciprocal influences of intraventricular infusions of NT-3 and BDNF in naïve and kindled hippocampi of rats using Western blotting. We confirm that hippocampal kindling resulted in a significant increase in levels of BDNF both in cytochrome C (control) infused and NT-3 infused kindled rats. However, NT-3 infusion significantly reduced BDNF levels in both kindled and non-kindled hippocampi compared to their cytochrome C infused counterparts. These results are consistent with our earlier studies demonstrating lowered levels of TrkA and TrkC (NGF modulates BDNF levels via TrkA) following chronic NT-3 infusion. Although kindling led to an increase in BDNF, this was not accompanied by any detectable change in the levels of proBDNF. However, there was a significant increase in proBDNF following NT-3 infusions, suggesting NT-3 may reduce proBDNF processing. In contrast, neither NT-3 nor proNT-3 levels were affected by kindling or chronic BDNF infusions, consistent with down-regulation of TrkB by chronic BDNF infusion. Thus, modulation of BDNF by NT-3, likely mediated by Trk receptors, occurs in naïve and kindled adult rat hippocampus.
Ullal
G R
GR
Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
Michalski
B
B
Xu
B
B
Racine
R J
RJ
Fahnestock
M
M
D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D003720:Densitometry; D015536:Down-Regulation / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism*; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D020933:Neurotrophin 3 / Q000502:physiology*; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D020917:Receptor, trkA / Q000378:metabolism; D020812:Receptor, trkC / Q000378:metabolism
D000199:Actins; D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D011498:Protein Precursors; C426674:brain-derived neurotrophic factor precursor; D045304:Cytochromes c; D020917:Receptor, trkA; D020812:Receptor, trkC