Trophic Effects of Brain-Derived Neurotrophic Factor Blockade in an Androgen-Sensitive Neuromuscular System

Abstract

In adult male rats, androgens are necessary for the maintenance of the motoneurons and their target muscles of the sexually dimorphic, steroid-sensitive spinal nucleus of the bulbocavernosus (SNB) neuromuscular system, regulating motoneuron and muscle morphology, function, and expression of trophic factors. Castration of males results in somal, dendritic, and muscle atrophy as well as increases in brain-derived neurotrophic factor (BDNF) in the target musculature. Because BDNF can have either facilitative or inhibitory effects in other systems, we examined SNB neuromuscular morphology after BDNF blockade using a fusion protein (tyrosine kinase receptor type B IgG). Blockade of BDNF in gonadally intact males resulted in hypertrophy of SNB motoneuron dendrites and target musculature, suggesting that normal levels of BDNF are inhibitory in SNB neuromuscular system. BDNF blockade in castrated males prevented SNB motoneuron atrophy and attenuated target muscle weight loss. This is the first demonstration that the highly androgen-sensitive SNB motoneuron dendrites and target muscles can be maintained in the absence of gonadal hormones and, furthermore, that blocking BDNF can have trophic effects on skeletal muscle. These results suggest that whereas BDNF is involved in the signaling cascade mediating the androgenic support of SNB neuromuscular morphology, its action can be inhibitory. Furthermore, the elevations in BDNF after castration may be responsible for the castration-induced atrophy in SNB motoneurons and target muscles, and the trophic effects of androgens may be mediated in part through a suppression of BDNF. These results may have relevance to therapeutic approaches to the treatment of neurodegenerative disease or myopathies.