Naturally occurring and axotomy-induced motoneuron death and its prevention by neurotrophic agents: a comparison...

Neuronal cell death is an important regressive event during the normal development of the peripheral and central nervous systems of many vertebrate and invertebrate species. Furthermore, when neurons are deprived of their target following axonal injury (axotomy) during embryonic, fetal, or early postnatal development, they undergo massive cell death. Both naturally occurring and axotomy-induced neuronal cell death can be prevented by treatment with growth factors or neurotrophic agents. Naturally occurring cell death of spinal MNs has been extensively studied in both avians and mammals. However, compared with mammals, there is little information on the effects of axotomy in avian species and it is not known whether trophic agents can modify axotomy-induced death in avian MNs. It is also not known whether trophic/growth factors can promote the in vivo survival of mammalian MNs during the period of naturally occurring cell death. We have examined (1) the time course of axotomy-induced death of lumbar spinal MNs in chick and mouse, and (2) the survival-promoting activity of a number of previously characterized growth and trophic factors on both programmed and axotomy-induced MN death in these two species. We show that axotomy performed on, or prior to, E12 in the chick results in a rapid decrease (i.e. 50%) in MN numbers within 3-4 days postsurgery, whereas these cells were able to survive for up to 1 week following axotomy on E14. By contrast, mouse MNs remained vulnerable to axotomy for at least 5 days after birth.(ABSTRACT TRUNCATED AT 250 WORDS)