title: Brain-derived neurotrophic factor supports facial motoneuron survival after facial nerve transection in immunodeficient mice.
abstract: Numerous studies have shown that motoneuron survival can be facilitated by neurotrophic factors (NTF) after injury. However, the ability of specific NTF to rescue facial motoneurons (FMN) from axotomy-induced death in immunodeficient mice has not been tested. Therefore, one goal of this study was to determine if brain-derived neurotrophic factor (BDNF), an NTF with a known ability to rescue FMN from axotomy-induced death, supports FMN from axotomy-induced death in recombinase activating gene-2 knockout (RAG-2 KO) mice that lack functional T and B lymphocytes. Nerve growth factor, which has been shown not to play a role in motoneuron survival, was used as a negative control. Brain derived neurotrophic factor treatment restored FMN survival to wild-type (WT) control levels 4 weeks post-operative (wpo) (80% +/- 1.9, 83% +/- 2.4, respectively). The second goal of this study was to begin to elucidate if CD4+ T cells produce NTF after facial nerve axotomy. Cervical lymph nodes were collected from WT mice 9 days post-operative, re-activated with anti-CD3 and supernatant collected 24 h later. Immediately after injury, the supernatant was administered to RAG-2 KO mice leading to an increase in FMN survival equivalent to WT controls (80% +/- 1.4, 84% +/- 2.1, respectively, 4 wpo). In addition, cervical lymph node supernatant treated with anti-BDNF attenuated FMN rescue in RAG-2 KO mice (62% +/- 3.3) 4 wpo. These data lend support to the hypothesis that CD4+ T cells produce NTF that support motoneuron survival before target reconnection occurs.
authors.affiliation: Rehabilitation, Research and Development Service, Hines VA Hospital, 5th and Roosevelt Road, Hines, IL 60141, USA. cserpe1@aol.com
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Serpe
authors.forename: Susanna C
authors.initials: SC
authors.lastname: Byram
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Sanders
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Jones
mesh_terms: D000818:Animals; D019771:Axotomy; D001402:B-Lymphocytes / Q000276:immunology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics; D005154:Facial Nerve / Q000166:cytology / Q000502:physiology*; D020220:Facial Nerve Injuries / Q000276:immunology / Q000503:physiopathology; D005260:Female; D016867:Immunocompromised Host; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009046:Motor Neurons / Q000166:cytology*; D009416:Nerve Regeneration / Q000276:immunology*; D015213:Neuroimmunomodulation / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2