Reciprocal changes in the expression of Bcl-2 and Bax in hypoglossal nucleus after axotomy in adult rats: possible involvement in the induction of neuronal cell death

Numerous studies of neonatal neuronal development in mammals have revealed that neuronal cell death following axotomy is apoptotic in nature. In adult animals, however, neuronal cell death following axonal injury may or may n ot exhibit features of apoptosis. Bcl-2 and Bar have been identified as inh ibitor and promoter proteins, respectively, of apoptosis. To investigate th e relationship between these proteins and neuronal cell death following axo tomy in adult animals, we performed axotomy of the right hypoglossal nerve in adult male Wister rats, and sacrificed the rats at various intervals aft er axotomy. We analyzed the expression of Bcl-2 and Bar immunohistochemical ly in the hypoglossal nuclei of the adult rats following axotomy. Our analy sis showed an increase in the percentage of Bar-positive motoneurons relati ve to the total number of motoneurons in the hypoglossal nucleus on the axo tomy side at three days after axotomy. In contrast, a low percentage of Bcl -2-positive motoneurons to the total number of motoneurons was noted at the same time interval after axotomy. Quantitative analysis of the signal inte nsity for Bcl-2 and Bar in individual neurons showed that Bar immunostainin g significantly increased 7 days after axotomy, while the intensity of Bcl- 2 immunostaining decreased in most of Bcl-2-positive neurons. Our results c onfirmed the occurrence of motoneuron cell death in adult rats after axotom y, and that a close temporal relationship exists between the reciprocal cha nges in Bcl-2/Bax expression and the loss of motoneurons. These results ind icate the possible involvement of the Bcl-2/Bax system in the induction of neuronal cell apoptosis after axotomy in adult rats. (C) 1999 Elsevier Scie nce B.V. All rights reserved.