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Protection from dendritic atrophy with testosterone following partial motoneuron depletion: dose-dependence in males and efficacy in females

Coons KD, Wilson RE, Sengelaub DR (2007) Protection from dendritic atrophy with testosterone following partial motoneuron depletion: dose-dependence in males and efficacy in females. Neuroscience 2007 Abstracts 56.11/S5. Society for Neuroscience, San Diego, CA.

Summary: Partial depletion of motoneurons from the highly androgen-sensitive spinal nucleus of the bulbocavernosus (SNB), or the more typical somatic motoneuron population innervating the quadriceps muscles, induces dendritic atrophy in remaining motoneurons. Treatment with testosterone (T) is neuroprotective, and dendritic atrophy following partial motoneuron depletion is attenuated in both populations. In the present study, we examined the dose-dependency of T effects in male rats, as well as its potential efficacy in females. Motoneurons innervating the bulbocavernosus/levator ani (BC/LA) or vastus medialis muscles were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Simultaneously, saporin-injected rats were given T implants designed to produce plasma titers ranging from 0.75 to 5.0 ng/ml or left untreated. Four weeks later, motoneurons innervating the contralateral BC or the ipsilateral vastus lateralis muscles were labeled with cholera toxin-conjugated HRP, and dendritic arbors were reconstructed in 3 dimensions. Partial motoneuron depletion resulted in dendritic atrophy in remaining SNB and quadriceps motoneurons (40% and 36% of normal length, respectively). T treatment attenuated this atrophy in a dose-dependent manner, with maximum effectiveness at 2.0-2.5 ng/ml (the normal adult physiological level). This dosage of T resulted in SNB dendritic lengths that did not differ from those of intact control males. In contrast, although dendritic atrophy in quadriceps motoneurons was attenuated by the same dosage of T, resultant dendritic lengths were 60% of normal length, and did not improve further with higher levels of T. Neuroprotective effects of T treatment were also assessed in quadriceps motoneurons in female rats (adult female rats lack the SNB neuromuscular system). As described above, motoneurons innervating the vastus medialis muscles were selectively killed by saporin injection, and females were given T implants (resulting in plasma levels of 2.0-2.5 ng/ml) or left untreated. Four weeks later, motoneurons innervating the ipsilateral vastus lateralis muscles were labeled with cholera toxin-conjugated HRP, and dendritic arbors were reconstructed. As in males, partial motoneuron depletion in females resulted in dendritic atrophy (52% of normal length) in remaining quadriceps motoneurons, and this atrophy was attenuated (70% of normal length) with T treatment. Together, these findings suggest that the neuroprotective effects of T on dendrites are achieved with dosages within the normal physiological range, and furthermore can be observed in motoneurons of both male and female rats.

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