PMID- 23512738 OWN - NLM STAT- MEDLINE DCOM- 20131113 LR - 20211021 IS - 1932-846X (Electronic) IS - 1932-8451 (Print) IS - 1932-8451 (Linking) VI - 73 IP - 8 DP - 2013 Aug TI - Androgen action at the target musculature regulates brain-derived neurotrophic factor protein in the spinal nucleus of the bulbocavernosus. PG - 587-98 LID - 10.1002/dneu.22083 [doi] AB - We have previously demonstrated that brain-derived neurotrophic factor (BDNF) interacts with testosterone to regulate dendritic morphology of motoneurons in the highly androgen-sensitive spinal nucleus of the bulbocavernosus (SNB). Additionally, in adult male rats testosterone regulates BDNF in SNB motoneurons and its target muscle, the bulbocavernosus (BC). Because BDNF is retrogradely transported from skeletal muscles to spinal motoneurons, we hypothesized that testosterone could regulate BDNF in SNB motoneurons by acting locally at the BC muscle. To test this hypothesis, we restricted androgen manipulation to the SNB target musculature. After castration, BDNF immunolabeling in SNB motoneurons was maintained at levels similar to those of gonadally intact males by delivering testosterone treatment directly to the BC muscle. When the same implant was placed interscapularly in castrated males it was ineffective in supporting BDNF immunolabeling in SNB motoneurons. Furthermore, BDNF immunolabeling in gonadally intact adult males given the androgen receptor blocker hydroxyflutamide delivered directly to the BC muscle was decreased compared with that of gonadally intact animals that had the same hydroxyflutamide implant placed interscapularly, or when compared with castrated animals that had testosterone implants at the muscle. These results demonstrate that the BC musculature is a critical site of action for the androgenic regulation of BDNF in SNB motoneurons and that it is both necessary and sufficient for this action. Furthermore, the local action of androgens at the BC muscle in regulating BDNF provides a possible mechanism underlying the interactive effects of testosterone and BDNF on motoneuron morphology. (c) 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 587-598, 2013. CI - Copyright (c) 2013 Wiley Periodicals, Inc. FAU - Verhovshek, Tom AU - Verhovshek T AD - Department of Neurological Surgery, Indiana Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, 46202, USA. tverhovs@indiana.edu FAU - Sengelaub, Dale R AU - Sengelaub DR LA - eng GR - R01 HD035315/HD/NICHD NIH HHS/United States PT - Journal Article DEP - 20130624 PL - United States TA - Dev Neurobiol JT - Developmental neurobiology JID - 101300215 RN - 0 (Androgens) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptors, Androgen) RN - 3XMK78S47O (Testosterone) SB - IM MH - Androgens/*metabolism MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Castration/adverse effects MH - Male MH - Motor Neurons/drug effects/*metabolism MH - Muscle, Skeletal/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Androgen MH - Spinal Cord/*metabolism MH - Testosterone/metabolism PMC - PMC4030717 MID - NIHMS578874 OTO - NOTNLM OT - SNB OT - bulbocavernosus OT - neurotrophic factors OT - testosterone EDAT- 2013/03/21 06:00 MHDA- 2013/11/14 06:00 PMCR- 2014/08/01 CRDT- 2013/03/21 06:00 PHST- 2012/12/20 00:00 [received] PHST- 2013/02/22 00:00 [revised] PHST- 2013/03/12 00:00 [accepted] PHST- 2013/03/21 06:00 [entrez] PHST- 2013/03/21 06:00 [pubmed] PHST- 2013/11/14 06:00 [medline] PHST- 2014/08/01 00:00 [pmc-release] AID - 10.1002/dneu.22083 [doi] PST - ppublish SO - Dev Neurobiol. 2013 Aug;73(8):587-98. doi: 10.1002/dneu.22083. Epub 2013 Jun 24.