Brain-derived neurotrophic factor and androgen interactions in spinal neuromuscular systems

Abstract

Neurotrophic factors and steroid hormones interact to regulate a variety of neuronal processes such as neurite outgrowth, differentiation, and neuroprotection. The coexpression of steroid hormone and neurotrophin receptor mRNAs and proteins, as well as their reciprocal regulation provides the necessary substrates for such interactions to occur. This review will focus on androgen-BDNF interactions in the spinal cord, describing androgen regulation of BDNF in neuromuscular systems following castration, androgen manipulation, and injury. Androgens interact with BDNF during development to regulate normally-occurring motoneuron death, and in adulthood, androgen-BDNF interactions are involved in the maintenance of several features of neuromuscular systems. Androgens regulate BDNF and trkB expression in spinal motoneurons. Androgens also regulate BDNF levels in the target musculature, and androgenic action at the muscle regulates BDNF levels in motoneurons. These interactions have important implications for the maintenance of motoneuron morphology. Finally, androgens interact with BDNF after injury, influencing soma size, dendritic morphology, and axon regeneration. Together, these findings provide further insight into the development and maintenance of neuromuscular systems and have implications for the neurotherapeutic/neuroprotective roles of androgens and trophic factors in the treatment of motoneuron disease and recovery from injury.

Androgen-dependent loss of muscle BDNF mRNA in two mouse models of SBMA

“…While the BDNF gene contains an estrogen response element (Sohrabji et al, 1995), there is no known androgen response element. One possible mechanism by which BDNF expression may be dysregulated in SBMA is through disruption of an AR regulated cyclic AMP-mediated pathway (reviewed in Verhovshek et al, 2013). …”

“…Because BDNF mediates effects of androgens on neuromuscular systems (Ottem et al, 2013; Verhovshek et al, 2013), and SBMA is an androgen-dependent neuromuscular disease, we examined BDNF expression and its androgen-dependence using quantitative polymerase chain reaction (qPCR) in two transgenic (Tg) mouse models of SBMA, the “97Q” and “myogenic” models.…”

Enhancement of peripheral nerve regeneration due to treadmill training and electrical stimulation is dependent on androgen receptor signaling

“…Based on the results presented above and those we have presented previously (Wilhelm et al, ; Wood et al, ), we conclude that the effectiveness of activity‐based therapies for promoting axon regeneration in injured peripheral nerves requires both an increase in BDNF expression in the neurons whose axons are regenerating and signaling through androgen receptors. The interaction of BDNF and its trkB receptor and androgens/androgen receptors in the mechanism underlying the effectivenss of these treatments is likely complex, as they show at least some capacity for regulating each other (Verhovshek et al, ). However, we feel that by identifying these requirements for activity‐based therapies and posing testable hypotheses, we have moved them closer to their translational potential.…”

Differential regulation of BDNF, synaptic plasticity and sprouting in the hippocampal mossy fiber pathway of male and female rats

“…The SNB motoneurons innervate the bulbocavernosus, levator ani, and external anal sphincter muscles, which are muscles that are required for male copulatory behavior. In the adult, androgens play an important role in the maintenance of SNB motorneurons because castration leads to atrophy of the SNB motorneuron somata and dendrites (for reviews, see Ottem et al, 2012; Verhovshek and Sengelaub et al, 2012). BDNF has been implicated in the supportive role of androgen on SNB motorneurons, but its interaction with androgen is complex.…”