PMID- 17462792 OWN - NLM STAT- MEDLINE DCOM- 20070726 LR - 20091119 IS - 0197-0186 (Print) IS - 0197-0186 (Linking) VI - 50 IP - 6 DP - 2007 May TI - NT-3 modulates BDNF and proBDNF levels in naive and kindled rat hippocampus. PG - 866-71 AB - 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 naive 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 naive and kindled adult rat hippocampus. FAU - Ullal, G R AU - Ullal GR AD - Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, Ontario L8N 3Z5, Canada. FAU - Michalski, B AU - Michalski B FAU - Xu, B AU - Xu B FAU - Racine, R J AU - Racine RJ FAU - Fahnestock, M AU - Fahnestock M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070307 PL - England TA - Neurochem Int JT - Neurochemistry international JID - 8006959 RN - 0 (Actins) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Neurotrophin 3) RN - 0 (Protein Precursors) RN - 0 (brain-derived neurotrophic factor precursor) RN - 9007-43-6 (Cytochromes c) RN - EC 2.7.10.1 (Receptor, trkA) RN - EC 2.7.10.1 (Receptor, trkC) SB - IM MH - Actins/metabolism MH - Animals MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology MH - Cytochromes c/metabolism MH - Densitometry MH - Down-Regulation/drug effects MH - Hippocampus/*metabolism MH - Kindling, Neurologic/*physiology MH - Male MH - Neurotrophin 3/*physiology MH - Protein Precursors/*metabolism MH - Rats MH - Rats, Long-Evans MH - Receptor, trkA/metabolism MH - Receptor, trkC/metabolism EDAT- 2007/04/28 09:00 MHDA- 2007/07/27 09:00 CRDT- 2007/04/28 09:00 PHST- 2006/11/03 00:00 [received] PHST- 2007/02/09 00:00 [revised] PHST- 2007/02/26 00:00 [accepted] PHST- 2007/04/28 09:00 [pubmed] PHST- 2007/07/27 09:00 [medline] PHST- 2007/04/28 09:00 [entrez] AID - S0197-0186(07)00059-9 [pii] AID - 10.1016/j.neuint.2007.02.009 [doi] PST - ppublish SO - Neurochem Int. 2007 May;50(6):866-71. doi: 10.1016/j.neuint.2007.02.009. Epub 2007 Mar 7.