CILIARY NEUROTROPHIC FACTOR MAINTAINS MOTONEURONS AND THEIR TARGET MUSCLES IN DEVELOPING RATS

Ciliary neurotrophic factor (CNTF) can enhance motoneuron survival dur ing naturally occurring cell death in the chick (Oppenheim et al., 199 1). Because receptors for CNTF are expressed in both motoneurons and t heir target muscles (Davis et al., 1991; Ip et al., 1993), both tissue s are potential sites of CNTF action in development. We examined the a bility of CNTF to prevent the degeneration of a neuromuscular system i n developing female rats. The death of motoneurons in the spinal nucle us of the bulbocavernosus (SNB) extends postnatally and is sexually di morphic, with many more motoneurons dying in females than in males. Th e bulbocavernosus (BC), a target muscle of SNB motoneurons, also degen erates postnatally in females. Female rats treated with daily injectio ns of 1 mug CNTF from embryonic day 22 through postnatal day 3 (P3) ha d 70% more SNB motoneurons on P4 than did control animals, and the num ber of pyknotic profiles in the SNB area was markedly reduced by CNTF. In addition, the degeneration of the BC was completely prevented by C NTF 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 m ay be a secondary consequence of effects on target muscles.