TRANSFORMING-GROWTH-FACTOR-ALPHA EXPRESSION AS A RESPONSE OF MURINE MOTOR-NEURONS TO AXONAL INJURY AND MUTATION-INDUCED DEGENERATION

We previously showed that degenerating adult motor neurons of the muri ne mutant wobbler, a model of spinal muscular atrophy, express Transfo rming Growth Factor alpha (TGF alpha), a growth factor endowed with gl io- and neurotrophic activities. Here, we evaluated whether TGF alpha expression is a general response of adult motor neurons to injury. Syn thesis of its precursor (pro-TGF alpha) was investigated in another mo del of motoneuronal degeneration, the murine mutant muscle deficient, and in hypoglossal motor neurons following axonal crush and cut. In co ntrol conditions, motor neurons were devoid of pro-TGF alpha. immunore activity. In the mutant lumbar spinal cord, pro-TGF alpha immunoreacti ve motor neurons appeared as soon as the disease developed and pro-TGF alpha expression persisted until the latest stages of degeneration. M otor neurons and astrocytes of the white matter weakly immunoreactive for the TGF alpha receptor were also present in both control and mutan t lumbar spinal cords. Following hypoglossal nerve crush and cut, moto neuronal pro-TGF alpha expression was precocious and transient, visibl e at one day post-injury and lasting for only 3 days, during which tim e astrocyte-like cells immunoreactive for both TGF alpha and its recep tor appeared within the injured nucleus. Enhanced TGF alpha mRNA level s following nerve crush showed that activation occurred at the transcr iptional level. These results show that upregulation of TGF alpha is a n early and common response of adult murine motor neurons to injury, r egardless of ita experimental or genetic origin.