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Testosterone fails to save androgen-sensitive rat motoneurons following early target removal
E M Kurz1, A R Cover, D R Sengelaub
1Program in Neural Science, Indiana University, Bloomington 47405.
Abstract:
Axotomy during development can result in the death of up to 100% of the affected motoneurons. However, axotomy-induced death can be significantly reduced by administration of androgens in young rats. Motoneuron death in the spinal nucleus of the bulbocavernosus (SNB) has previously been shown to be regulated by androgens during development. the present experiment examined the effects of androgen treatment on the survival of SNB motoneurons after target removal and concomitant axotomy early in development. On the day of birth, two target muscles of SNB motoneurons of male and female rats were bilaterally extirpated. Target removal resulted in a dramatic loss of SNB motoneurons within 48 h of surgery, with an ultimate loss of virtually all motoneurons projecting to the extirpated muscles by postnatal day 10. Treatment with testosterone failed to save SNB motoneurons from target removal-induced death. Pups treated with testosterone after target removal did not differ in the pattern or timing of motoneuron loss from untreated pups at any age examined. Counts of degenerating cells in the SNB reflected the extensive motoneuron loss and also did not differ with testosterone treatment. These results indicate that testosterone cannot save the androgen-sensitive SNB motoneurons from death after target removal and concomitant axotomy early in development. The failure of testosterone treatment to rescue SNB motoneurons in the absence of the SNB target musculature further suggests that during normal development, both androgens and target muscles are necessary for SNB motoneuron survival.
Insights
Androgen treatment does not prevent motoneuron death after target muscle removal in developing rats. Both androgens and target muscles are crucial for motoneuron survival during development.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Axotomy, or nerve injury, during development can lead to motoneuron death.
- Androgens are known to promote motoneuron survival.
- The spinal nucleus of the bulbocavernosus (SNB) motoneurons are androgen-sensitive.
Purpose of the Study:
- To investigate the effect of androgen (testosterone) treatment on SNB motoneuron survival following target muscle removal and axotomy in early development.
- To determine if testosterone can rescue SNB motoneurons when their target muscles are absent.
Main Methods:
- Surgical removal of target muscles for SNB motoneurons in newborn male and female rats.
- Administration of testosterone treatment post-surgery.
- Quantification of SNB motoneuron survival and degeneration at various postnatal ages.
Main Results:
- Target muscle removal caused significant SNB motoneuron loss within 48 hours, with near-complete loss by postnatal day 10.
- Testosterone treatment did not prevent or reduce motoneuron death following target removal.
- Degenerating cell counts confirmed extensive motoneuron loss, unaffected by testosterone administration.
Conclusions:
- Testosterone cannot rescue androgen-sensitive SNB motoneurons from death when their target musculature is removed early in development.
- Normal development of SNB motoneurons requires both androgen signaling and the presence of their target muscles.
- These findings highlight the critical interplay between hormonal and target-derived factors in ensuring motoneuron survival.