title: Neuroprotective effects of testosterone metabolites and dependency on receptor action on the morphology of somatic motoneurons following the death of neighboring motoneurons.
abstract: Partial depletion of spinal motoneuron populations induces dendritic atrophy in neighboring motoneurons, and treatment with testosterone is neuroprotective, attenuating induced dendritic atrophy. In this study we examined whether the protective effects of testosterone could be mediated via its androgenic or estrogenic metabolites. Furthermore, to assess whether these neuroprotective effects were mediated through steroid hormone receptors, we used receptor antagonists to attempt to prevent the neuroprotective effects of hormones after partial motoneuron depletion. Motoneurons innervating the vastus medialis muscles of adult male rats were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Simultaneously, some saporin-injected rats were treated with either dihydrotestosterone or estradiol, alone or in combination with their respective receptor antagonists, or left untreated. 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 intact normal animals, partial motoneuron depletion resulted in decreased dendritic length in remaining quadriceps motoneurons. Dendritic atrophy was attenuated with both dihydrotestosterone and estradiol treatment to a degree similar to that seen with testosterone, and attenuation of atrophy was prevented by receptor blockade. Together, these findings suggest that neuroprotective effects on motoneurons can be mediated by either androgenic or estrogenic hormones and require action via steroid hormone receptors, further supporting a role for hormones as neurotherapeutic agents in the injured nervous system. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 691-707, 2017.
authors: Program in Neuroscience and Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, 47405.
authors: Yi
authors: Y
authors: Cai
authors: Program in Neuroscience and Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, 47405.
authors: Cory
authors: C
authors: Chew
authors: Program in Neuroscience and Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, 47405.
authors: Fernando
authors: F
authors: Muñoz
authors: Program in Neuroscience and Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, 47405.
authors: Dale R
authors: DR
authors: Sengelaub
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002772:Cholera Toxin / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology; D005485:Flutamide / Q000494:pharmacology; D006735:Horseradish Peroxidase / Q000378:metabolism; D008297:Male; D009046:Motor Neurons / Q000166:cytology* / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000726:Androgen Antagonists; D018696:Neuroprotective Agents; D011944:Receptors, Androgen; C052635:cholera toxin, B subunit-horseradish peroxidase; D013196:Dihydrotestosterone; D013629:Tamoxifen; D013739:Testosterone; D005485:Flutamide; D002772:Cholera Toxin; D006735:Horseradish Peroxidase
keywords: dendrites; morphology; neuroprotection; steroids