No abstract

Feral white-footed mice are seasonal breeders that undergo predictable cycles of reproductive function. Photoperiod-induced fluctuations in gonadal function of white-footed mice were associated with morphological changes in perineal muscles and their motoneurons. Exposure to short daylengths resulted in testicular regression, decreased perineal muscle mass, and shrinkage of somata and nuclei of motoneurons of the spinal nucleus of the bulbocavernosus (SNB). These effects were reversed by reinstatement of long daylengths. Similar reductions in muscle mass and SNB soma size were seen following gonadectomy of white-footed mice. In addition, dendritic trees of SNB motoneurons were reduced in gonadectomized mice compared with dendritic arbors of intact mice or castrates provided with testosterone capsules. Androgen-mediated annual changes in muscle mass and motoneuron morphology appear to be a natural part of this species' physiology.

Ciliary neutrophic factor (CNTF) can enhance motoneuron survival during naturally occurring cell death in the chick (Oppenheim et al, 1991). Because receptors for CNTF are expressed in both motoneurons and their target muscles (Davis et al., 1991; lp et al., 1993), both tissues are potential sites of CNTF action in development. We examined the ability of CNTF to prevent the degeneration of a neuromuscular system in developing female rats. The death of motoneurons in the spinal nucleus of the bulbocavernosus (SNB) extends postnatally and is sexually dimorphic, with many more motoneurons dying in females than in males. The bulbocavernosus (BC), a target muscle of SNB motoneurons, also degenerates postnatally in females. Female rats treated with daily injections of 1 microgram CNTF from embryonic day 22 through postnatal day 3 (P3) had 70% more SNB motoneurons on P4 than did control animals, and the number of pyknotic profiles in the SNB area was markedly reduced by CNTF. In addition, the degeneration of the BC was completely prevented by CNTF treatment of perinatal female rats. These results demonstrate that CNTF can preserve mammalian motoneurons from developmental death, but also suggest that the sparing effect of CNTF on motoneurons in vivo may be a secondary consequence of effects on target muscles.

A sexual dimorphism in the number of motoneurons in the spinal nucleus of the bulbocavernosus (SNB) of rats is engendered by a sex difference in ontogenetic cell death. Testicular secretions, specifically androgenic steroids, reduce SNB motoneuron death in males. The fate of the target muscles generally mirrors that of the motoneurons, and androgens appear to exert their effects upon the target muscles, sparing the motoneurons as a secondary consequence. Treatment with ciliary neurotrophic factor can also spare SNB motoneurons in newborn females, raising the possibility that this factor normally mediates androgen's effect upon motoneuron survival. The ontogeny of calcitonin gene-related peptide immunoreactivity is delayed in SNB cells compared with other motoneurons and is further delayed in the SNB cells of females. In both sexes, calcitonin gene-related peptide is detected after the period of SNB motoneuron death is complete. A sex difference in motoneuron number is also seen in the human homologue of the SNB and, because ontogenetic death of motoneurons in humans overlaps the period of androgen secretion, may arise in a manner similar to that in the rat SNB.

Immunoreactivity for calcitonin gene-related peptide (CGRP) has been observed in both adult and embryonic rat motoneurons. However, the developmental pattern of CGRP expression in motoneurons has not been systematically examined and the role of CGRP in neuromuscular development is poorly understood. We have mapped the ontogeny of CGRP-like immunoreactivity in three motoneuron pools of the rat lumbar spinal cord from birth through adulthood. Immunoreactivity was uniformly high in lateral horn motoneurons (the retrodorsolateral nucleus) of males and females at all ages examined. The majority of motoneurons of the dorsolateral nucleus also were positive throughout postnatal development although the percentage of positive motoneurons was slightly higher in males than in females. In contrast, virtually no motoneurons of the spinal nucleus of the bulbocavernosus, located in the medial ventral horn, were positive for CGRP in neonatal rats. CGRP-like immunoreactivity was delayed in this nucleus until approximately postnatal day 6 in males and day 27 in females. Because these three motoneuronal nuclei are differentially sensitive to early androgen and differ with respect to the timing of several developmental milestones, these observations have implications for the regulation and possible roles of CGRP in developing motor systems.