PMID- 19427307 OWN - NLM STAT- MEDLINE DCOM- 20100416 LR - 20131121 IS - 1090-2430 (Electronic) IS - 0014-4886 (Linking) VI - 223 IP - 1 DP - 2010 May TI - Electrical stimulation and testosterone differentially enhance expression of regeneration-associated genes. PG - 183-91 LID - 10.1016/j.expneurol.2009.04.031 [doi] AB - As functional recovery following peripheral nerve injury is dependent upon successful repair and regeneration, treatments that enhance different regenerative events may be advantageous. Using a rat facial nerve crush axotomy model, our lab has previously investigated the effects of a combinatorial treatment strategy, consisting of electrical stimulation (ES) of the proximal nerve stump and testosterone propionate (TP) administration. Results indicated that the two treatments differentially enhance facial nerve regenerative properties, whereby ES reduced the delay before sprout formation, TP accelerated the overall regeneration rate, and the combinatorial treatment had additive effects. To delineate the molecular mechanisms underlying such treatments, the present study investigated the effects of ES and TP on expression of specific regeneration-associated genes. Following a right facial nerve crush at the stylomastoid foramen, gonadectomized adult male rats were administered only ES, only TP, a combination of both, or left untreated. Real time RT-PCR analysis was used to assess fold changes in mRNA levels in the facial motor nucleus at 0 h, 6 h, 1 d, 2 d, 7 d, and 21 d post-axotomy. The candidate genes analyzed included two tubulin isoforms (alpha(1)-tubulin and beta(II)-tubulin), 43-kiloDalton growth-associated protein (GAP-43), brain derived neurotrophic factor (BDNF), pituitary adenylate cyclase-activating peptide (PACAP), and neuritin (candidate plasticity-related gene 15). The two treatments have differential effects on gene expression, with ES leading to early but transient upregulation and TP producing late but steady increases in mRNA levels. In comparison to individual treatments, the combinatorial treatment strategy has the most enhanced effects on the transcriptional program activated following injury. CI - Copyright 2009 Elsevier Inc. All rights reserved. FAU - Sharma, Nijee AU - Sharma N AD - Neuroscience Program, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA. nijeesharma@gmail.com FAU - Marzo, Sam J AU - Marzo SJ FAU - Jones, Kathryn J AU - Jones KJ FAU - Foecking, Eileen M AU - Foecking EM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090507 PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 RN - 0 (Androgens) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (GAP-43 Protein) RN - 0 (Pituitary Adenylate Cyclase-Activating Polypeptide) RN - 0 (Protein Isoforms) RN - 0 (RNA, Messenger) RN - 0 (Tubulin) RN - WI93Z9138A (Testosterone Propionate) SB - IM MH - Analysis of Variance MH - Androgens/*therapeutic use MH - Animals MH - Axotomy/methods MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Disease Models, Animal MH - Electric Stimulation/*methods MH - Facial Nerve Diseases/*therapy MH - GAP-43 Protein/genetics/metabolism MH - Gene Expression Regulation/*drug effects MH - Male MH - Nerve Regeneration/*drug effects/physiology MH - Neuritis/genetics/metabolism MH - Orchiectomy/methods MH - Pituitary Adenylate Cyclase-Activating Polypeptide/genetics/metabolism MH - Protein Isoforms/genetics/metabolism MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Testosterone Propionate/*therapeutic use MH - Time Factors MH - Tubulin/genetics/metabolism EDAT- 2009/05/12 09:00 MHDA- 2010/04/17 06:00 CRDT- 2009/05/12 09:00 PHST- 2009/03/30 00:00 [received] PHST- 2009/04/26 00:00 [revised] PHST- 2009/04/28 00:00 [accepted] PHST- 2009/05/12 09:00 [entrez] PHST- 2009/05/12 09:00 [pubmed] PHST- 2010/04/17 06:00 [medline] AID - S0014-4886(09)00180-0 [pii] AID - 10.1016/j.expneurol.2009.04.031 [doi] PST - ppublish SO - Exp Neurol. 2010 May;223(1):183-91. doi: 10.1016/j.expneurol.2009.04.031. Epub 2009 May 7.