Kiley BJ, Sengelaub DR (2015) Neuroprotection with androgens following partial motoneuron depletion: A role for microglia. Neuroscience 2015 Abstracts 689.18/K11. Society for Neuroscience, Chicago IL.
Summary: Neurodegenerative disease or nerve injury results in the loss of spinal motoneurons, and remaining motoneurons show a variety of morphological and functional changes. We have previously demonstrated that partial depletion of motoneurons innervating the quadriceps muscles induces dendritic atrophy in remaining motoneurons, with 70% decreases in dendritic length. Treatment with testosterone is neuroprotective, and dendritic atrophy following partial motoneuron depletion is attenuated. In the present study, we explored a potential mechanism for this induced atrophy and the protection by androgen treatment, examining the response of microglia to the partial depletion of motoneurons with and without testosterone treatment. Microglia are activated locally and recruited from other sites in response to injury. Microglia are involved in the removal of synapses and dendrites after injury, and there is evidence that their activation is influenced by steroid hormones. Motoneurons innervating the vastus medialis muscle in adult male rats were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Simultaneously, saporin-injected rats were given systemic treatments via interscapular implants containing testosterone or left blank. One or three weeks later, microglia were visualized after immunohistochemical staining for Iba1. Microglia surrounding the injured motoneurons were classified as monitoring or activated (primed, reactive, or ameboid) based on morphology and counted stereologically. Compared with intact males, partial motoneuron depletion resulted in increases in the total number of microglia (78% and 24% at 1 and 3 weeks post-saporin, respectively) in the quadriceps motor pool. These changes were driven by increases in the number of activated microglia compared to levels found in intact animals; the number of activated microglia increased by 144% at 1 week post-saporin, and remained elevated at 3 weeks (51%). The increases in the number of activated microglia were attenuated with testosterone treatment; the number of activated forms increased only 34% and 17% at 1 and 3 weeks post-saporin, respectively. These findings suggest that the dendritic atrophy observed in remaining motoneurons after partial motoneuron depletion could be a result of increased microglial activation in the injury site, resulting in collateral damage through synaptic stripping and dendritic loss. The attenuation of both dendritic atrophy and microglial activation with testosterone treatment supports this potential causal effect, and further supports a role for hormones as neurotherapeutic agents in the injured nervous system.
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