DIFFERENTIAL REGULATION OF MOTOR-NEURON SURVIVAL AND CHOLINE-ACETYLTRANSFERASE EXPRESSION FOLLOWING AXOTOMY

Although it is well known that motor neuron survival following axotomy is enhanced with maturation, the ability of surviving neurons to expr ess the cholinergic enzyme choline acetyltransferase (ChAT) following axotomy has not been closely examined. Moreover, the utility of the fa cial nucleus in studies of motoneuron response to injury and to trophi c factors, coupled with the increasing importance of the mouse in gene targeting, compelled us to investigate the age dependence of neuronal survival and ChAT expression in the mouse facial nucleus following ax otomy. We cut the facial nerve at postnatal day (P) 4, 7, 14, 21, and 28 or in the adult and used Nissl staining and ChAT immunocytochemistr y to quantitate survival and ChAT expression, respectively, following 1, 2, or 3 weeks' survival at each age. We confirm in this model that the rate and extent of motor neuron death following axotomy is reduced with increasing maturity. The surviving neurons maintain a high ChAT content through P21; however, axotomy from P28 through adulthood resul ts in a striking reduction in ChAT immunoreactivity. That is, although axotomy at P21 results in 61% motor neuron survival, with virtually a ll of the surviving neurons being ChAT positive, axotomy in the adult results in 72% survival but only 9% of the neurons are ChAT positive. Thus, surviving motor neurons in the adult animals are only weakly cho linergic. These results indicate that a change in the regulation of Ch AT expression occurs following P21 so that cell survival and enzyme le vels are uncoupled. We suggest that the putative factor or factors tha t enhances motor neuron survival in maturity is not capable of maintai ning ChAT expression. (C) 1995 John Wiley and Sons, Inc.