Coons KD, Sengelaub DR (2008) Protection from dendritic atrophy with testosterone following partial motoneuron depletion: Timing and duration of treatment, functional correlates in motor activation. Neuroscience 2008 Abstracts 556.23/CC10. Society for Neuroscience, Washington, DC.
Summary: We have previously demonstrated that partial depletion of motoneurons innervating the quadriceps muscles induces dendritic atrophy in remaining motoneurons; this atrophy can be attenuated in a dose-dependent fashion, and in both male and female rats, with testosterone (T) treatment. In the present study, we examined (1) how the timing and duration of T treatment affect its ability to attenuate induced atrophy in remaining quadriceps motoneurons, and (2) the effects of induced atrophy and T treatment on subsequent motor function in male rats. Motoneurons innervating the vastus medialis muscles were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Rats were then treated with supplemental T at different times post-saporin injection (immediately, or at 2 or 3 weeks), or for different durations (1, 2, 3, or 4 weeks) or left untreated. All T treatments consisted of subcutaneous implants designed to produce plasma titers in the normal physiological range. Following treatment, the morphology of motoneurons innervating the ipsilateral vastus lateralis muscles was examined using retrograde labeling with cholera toxin-conjugated HRP. In a separate set of rats, quadriceps motoneuron activation was assessed using peripheral nerve recording. Motoneuron morphology and motor activation were also assessed in a group of untreated normal males. Partial motoneuron depletion resulted in dendritic atrophy in remaining quadriceps motoneurons. Treatment with T attenuated this atrophy, but in a time-sensitive manner. Four weeks of T treatment (delivered immediately post-saporin), or two weeks of T treatment (after a delay of two weeks post-saporin) were both effective in attenuating induced dendritic atrophy. However, dendritic atrophy in animals with immediate T treatment of shorter durations or longer delays in the start of treatment was comparable to that of animals who received no supplemental T. Consistent with the morphological changes, partial motoneuron depletion in otherwise untreated males resulted in deficits in motor activation: activation of quadriceps motoneurons required greater stimulus intensities and resulted in decreased amplitudes of motor nerve activity. Importantly, just as observed for dendritic morphology, these changes were attenuated by treatment with supplemental T. These results demonstrate that the neuroprotective effect of T on motoneuron morphology is more dependent on the timing of treatment than on its duration, and also provide a functional correlate of the morphological effects of that treatment, further supporting a role for T as a neurotherapeutic agent in the injured nervous system.
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