Androgen-dependent regulation of brain-derived neurotrophic factor and tyrosine kinase B in the sexually dimorphic spinal nucleus of the bulbocavernosus.
Castration of adult male rats causes the dendrites of androgen-sensitive motoneurons of the spinal nucleus of the bulbocavernosus (SNB) to retract. Brain-derived neurotrophic factor (BDNF), via activation of tyrosine receptor kinase B (trkB), has been implicated in mediating androgen effects on SNB dendrites. We used in situ hybridization to demonstrate that SNB motoneurons in gonadally intact adult male rats contain mRNA for both BDNF and trkB. Two weeks after gonadectomy, both transcripts were significantly decreased in SNB motoneurons but not in the non-androgen-responsive motoneurons of the adjacent retrodorsolateral nucleus (RDLN). In a second experiment, target perineal and foot muscles of SNB and RDLN motoneurons, respectively, were injected with the retrograde tracer Fluorogold, and then immunocytochemistry was performed to examine the distribution of BDNF and trkB proteins in SNB and RDLN motoneurons and their glutamatergic afferents. Confocal analysis revealed that gonadectomy induces a loss of BDNF protein in SNB dendrites but not in RDLN dendrites. Testosterone treatment of castrates prevented the loss of BDNF from SNB dendrites. Confocal analysis also revealed trkB protein in SNB and RDLN dendrites and in their glutamatergic afferents. Gonadectomy had no discernable effect on trkB protein in SNB or RDLN motoneurons or in their glutamatergic afferents. These results suggest that androgen maintains a BDNF-signaling pathway in SNB motoneurons that may underlie the maintenance of dendritic structure and synaptic signaling.
Ottem
Erich N
EN
Neuroscience Program, 108 Giltner Hall, Michigan State University, East Lansing, Michigan 48824, USA. ottem@msu.edu
Beck
Laurel A
LA
Jordan
Cynthia L
CL
Breedlove
S Marc
SM
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003712:Dendrites / Q000502:physiology; D005456:Fluorescent Dyes; D018698:Glutamic Acid / Q000502:physiology; D008161:Lumbosacral Region; D008297:Male; D009046:Motor Neurons / Q000502:physiology* / Q000648:ultrastructure; D009475:Neurons, Afferent / Q000502:physiology / Q000648:ultrastructure; D009919:Orchiectomy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000235:genetics*; D012727:Sex Characteristics; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D013266:Stilbamidines
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D000728:Androgens; D019208:Brain-Derived Neurotrophic Factor; D005456:Fluorescent Dyes; D012333:RNA, Messenger; D013266:Stilbamidines; D018698:Glutamic Acid; D020813:Receptor, trkB