Naturally occurring cell death and differentiation of developing spinal motoneurons following axotomy

Abstract

The purpose of this study was to examine the effects of axon transection on the development and differentiation of spinal motoneurons in the bullfrog (Rana catesbeiana) tadpole. The 3 ventral roots (VRs) that innervate the hindlimb were transected, and the animals were killed 6-7 weeks later (reinnervation took place within 3 weeks). At early stages of development, axotomy resulted in an increase in the number of spinal motoneurons on the operated side. By histological criteria, these motoneurons appeared more differentiated than those in normal tadpoles. Axotomy was effective in increasing motoneuron number only during the period of naturally occurring cell death. Similar effects were seen when the transected VRs were ligated to prevent regeneration. Hindlimb amputation without VR transection had no effect on motoneuron number or differentiation. Thus, target removal is neither a necessary nor a sufficient condition for hyperplasia of the lateral motor column. An extreme loss of spinal motoneurons was seen if the operated tadpole entered into metamorphic climax during the 6-7-week postoperative survival period. Motoneuron loss occurred although the injured motoneurons had reconnected to the hindlimb. In contrast, tadpoles allowed to survive up to 6 months showed no loss of motoneurons if they did not enter metamorphic climax. From these data, it appears axon transection in developing spinal motoneurons exerts its effects on motoneuron number and differentiation by altering the metabolic state of the motoneuron (axon reaction) rather than by depriving it of contact with its target.

Axotomy‐induced neuronal death during development

“…In a species which spends a prolonged period in a larval stage, Rana catesbeiana, transection of ventral. roots prior to metamorphosis prevents rather than exacerbates naturally occumng motor neuron death (Farel, 1989). Transection of motor axons at a distal site by target removal has no effect on motor neurons prior to metamorphosis in this species.…”

“…Another hypothesis suggests that effects of axotomy are not due to deprivation of target-derived growth factors but that axotomy renders neurons particularly vulnerable to deleterious effects of neuronal activity that might be mediated via the actions of excitatory amino acids (Lowrie and Vrbova, 1992; see also Farel, 1989). If this idea were correct, then one might expect that deafferentation could partially offset the deleterious effects of axotomy and diminish the extent of naturally occurring cell death; however, contrary to the expectations of this hypothesis, iri avian and mammalian preparations, deafferentation typically leads to substantial and sometimes massive cell death, either when performed alone or in combination with axotomy (see above; see also Clarke and Egloff, 1988).…”

Sensory neuron number in neonatal and adult rats estimated by means of stereologic and profile‐based methods

“…In the larval frog, type-L motoneurons appear more mature following axotomy (Farel, 1989); this raises the further possibility that manipulations that appear to affect neuron number may instead be altering the appearance of incompletely differentiated neurons such that they now meet the criteria for counting. Previous work on frogs supports the hypothesis that the apparent increase in neuron number is due to the late differentiation of neurons that are not recognized in counts performed on young animals.…”

Sensory neuron number in neonatal and adult rats estimated by means of stereologic and profile-based methods

“…The existence of these type-L neurons in the DRGs of young animals may influence the validity of conclusions concerning postnatal changes in neuron number. In the larval frog, type-L motoneurons appear more mature following axotomy (Farel, 1989); this raises the further possibility that manipulations that appear to affect neuron number may instead be altering the appearance of incompletely differentiated neurons such that they now meet the criteria for counting.…”