Chew C, Sengelaub DR (2019) Exercise is neuroprotective following partial motoneuron depletion via androgen action at the target muscle. Neuroscience 2019 Abstracts 134.13. Society for Neuroscience, Chicago, IL.
Summary: We have previously demonstrated that partial depletion of motoneurons innervating the quadriceps muscles induces dendritic atrophy in remaining motoneurons. Furthermore, systemic treatment with supplemental androgens is neuroprotective, and dendritic atrophy following partial motoneuron depletion is attenuated. Blockade of the androgen receptor at the target muscle prevents the neuroprotective effects on motoneuron dendrites in rats treated with supplemental androgens. We have recently shown that exercise is also neuroprotective on motoneuron dendrites following partial motoneuron depletion, and circulating levels of androgens have previously been shown to increase following exercise. Together, these results suggest that exercise may be neuroprotective via androgen action at the muscle. In the present study, we examine whether blockade of androgen receptors at the target musculature would prevent the neuroprotective effects of exercise on dendrites following partial motoneuron depletion. Motoneurons innervating the vastus medialis muscle in adult male rats were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Simultaneously, some saporin-injected rats were given implants of the androgen receptor antagonist hydroxyflutamide, either directly at the quadriceps musculature or interscapularly as a systemic control. Following saporin injections, some animals were allowed free access to running wheels attached to their home cages. Four weeks later, motoneurons innervating the ipsilateral vastus lateralis muscle were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. Compared with untreated males, partial motoneuron depletion resulted in decreased dendritic length in remaining quadriceps motoneurons. Early data suggests that following partial motoneuron depletion, exercised males with androgen receptor blockade at the quadriceps show dendritic lengths that are significantly shorter than those of exercised males with no treatment, while dendritic lengths in exercised males with interscapular implants do not differ from those of exercised animals without implants. These findings suggest that exercise may be protective against dendritic atrophy via androgens binding at the target musculature.
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