Temporal Correlation of Bax Expression and Axotomy-Induced Motoneuronal Apoptosis in Adult Rats: A Morphometric, Ultrastructural and Immunohistochemical Study

As apoptotic cell death is extremely involved in physiological development and many pathological situations such as cancer and neurodegenerative diseases, the understanding of its molecular machinery can be useful in designing new therapeutic strategies. The present study investigated the temporal expression of the proapoptotic protein Bax in adult spinal motoneurons. Following unilateral mid-thigh sciatic transection in adult rats, the incidence and nature of spinal motoneuron loss were evaluated by means of light microscopic cell count and electron microscopy 1 day, 1 week, 1 month and 3 months post-operatively. In all groups the temporal expression of Bax was immunohistochemically determined and the findings were compared with the results of the cell count. Following axotomy the related motoneurons underwent chromatolytic changes which increased up to one month and diminished in the 3-month group. One day following axotomy the number of motoneurons did not show any significant reduction, but thereafter a progressive cell loss occurred, which was most prominent after three months. Electron microscopic study confirmed the ultrastructural apoptotic nature of cell death. Bax immunohistochemistry indicated an increasing immunoreactivity up to one month post-axotomy, but in 3-month group it was clearly diminished. Following transection of a peripheral nerve in adult animals, related motoneurons undergo chromatolytic changes which in some neurons may proceed to apoptotic cell death. Although the proapoptotic protein Bax has long been believed as the main apoptotic factor, other Bax-independent pathways may also participate in the axotomy-induced neuronal apoptosis which must not be ignored.