Blockade of endogenous neurotrophic factors prevents the androgenic rescueof rat spinal motoneurons

Target-derived neurotrophic factors are assumed to regulate motoneuron cell death during development but remain unspecified. Motoneuron cell death in the spinal nucleus of the bulbocavernosus (SNB) of rats extends postnatally and is controlled by androgens. We exploited these features of the SNB sys tem to identify endogenously produced trophic factors regulating motoneuron survival. Newborn female rat pups were treated with the androgen, testoste rone propionate, or the oil vehicle alone. In addition, females received tr ophic factor antagonists delivered either into the perineum (the site of SN B target muscles) or systemically. Fusion molecules that bind and sequester the neurotrophins (trkA-IgG, trkB-IgG, and trkC-IgG) were used to block ac tivation of neurotrophin receptors, and AADH-CNTF was used to antagonize si gnaling through the ciliary neurotrophic factor receptor-alpha (CNTFR alpha ). An acute blockade of trkB, trkC, or CNTFR alpha prevented the androgenic sparing of SNB motoneurons when antagonists were delivered to the perineum . Trophic factor antagonists did not significantly reduce SNB motoneuron nu mber when higher doses were injected systemically. These findings demonstra te a requirement for specific, endogenously produced trophic factors in the androgenic rescue of SNB motoneurons and further suggest that trophic fact or interactions at the perineum play a crucial role in masculinization of t his neural system.