PMID- 18430030 OWN - NLM STAT- MEDLINE DCOM- 20080701 LR - 20201209 IS - 1460-9568 (Electronic) IS - 0953-816X (Linking) VI - 27 IP - 9 DP - 2008 May TI - Differential effects of pro-BDNF on sensory neurons after sciatic nerve transection in neonatal rats. PG - 2380-90 LID - 10.1111/j.1460-9568.2008.06215.x [doi] AB - Brain-derived neurotrophic factor (BDNF) plays a critical role in the development of the central and peripheral nervous systems, and also in neuronal survival after injury. The actions of BDNF are mediated by its high-affinity receptors TrkB and p75NTR. Recent studies have shown that proneurotrophins bind p75NTR and sortilin with high affinity, and trigger apoptosis of neurons in vitro. As proneurotrophins are a dominant form of gene products in developing and adult animals, it is imperative to understand their physiological functions in animals. Here, we showed differential roles of proBDNF in injured and uninjured sensory neurons. proBDNF, p75NTR and sortilin are highly expressed in dorsal root ganglia (DRG) neurons. Recombinant proBDNF induced a dose-dependent death of PC12 cells and the death activity was completely abolished in the presence of antibodies against the prodomain of BDNF. The exogenous proBDNF enhanced the death of axotomized sensory neurons and the neutralizing antibodies to the prodomain or exogenous sortilin-extracellular domain-Fc fusion molecule reduced the death of axotomized sensory neurons. Interestingly, the treatment of neutralizing antibody in vivo increased the number of sensory neurons in the contralateral DRG. We conclude that proBDNF may induce the death of axotomized sensory neurons and suppress neuronal addition in the intact DRG in neonatal rats, and the suppression of endogenous proBDNF may protect neurons after neurotrauma. FAU - Fan, Yong-Jun AU - Fan YJ AD - Department of Human Physiology and Centre for Neuroscience, Flinders University, GPO Box 2100, Adelaide, SA 5001, Australia. FAU - Wu, Linda Lin-Yan AU - Wu LL FAU - Li, Hong-Yun AU - Li HY FAU - Wang, Yan-Jiang AU - Wang YJ FAU - Zhou, Xin-Fu AU - Zhou XF LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080422 PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Adaptor Proteins, Vesicular Transport) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Membrane Glycoproteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Protein Precursors) RN - 0 (Receptors, Growth Factor) RN - 0 (Receptors, Nerve Growth Factor) RN - 0 (Recombinant Proteins) RN - 0 (brain-derived neurotrophic factor precursor) RN - 136958-07-1 (Ngfr protein, rat) RN - Z020Y8WIJ4 (sortilin) SB - IM MH - Adaptor Proteins, Vesicular Transport MH - Animals MH - Animals, Newborn MH - Apoptosis/physiology MH - Axotomy MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Functional Laterality MH - Ganglia, Spinal/metabolism MH - Immunohistochemistry MH - Membrane Glycoproteins/biosynthesis MH - Nerve Tissue Proteins/biosynthesis MH - Neurons, Afferent/*metabolism/pathology MH - Protein Precursors/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Growth Factor MH - Receptors, Nerve Growth Factor/biosynthesis MH - Recombinant Proteins MH - Sciatic Nerve/pathology/*physiology EDAT- 2008/04/24 09:00 MHDA- 2008/07/02 09:00 CRDT- 2008/04/24 09:00 PHST- 2008/04/24 09:00 [pubmed] PHST- 2008/07/02 09:00 [medline] PHST- 2008/04/24 09:00 [entrez] AID - EJN6215 [pii] AID - 10.1111/j.1460-9568.2008.06215.x [doi] PST - ppublish SO - Eur J Neurosci. 2008 May;27(9):2380-90. doi: 10.1111/j.1460-9568.2008.06215.x. Epub 2008 Apr 22.