Transforming growth factor α expression as a response of murine motor neurons to axonal injury and mutation-induced degeneration

Abstract

We previously showed that degenerating adult motor neurons of the murine mutant wobbler, a model of spinal muscular atrophy, express Transforming Growth Factor α (TGFα), a growth factor endowed with glio- and neurotrophic activities. Here, we evaluated whether TGFα expression is a general response of adult motor neurons to injury. Synthesis of its precursor (pro-TGFα) was investigated in another model of motoneuronal degeneration, the murine mutant muscle deficient, and in hypoglossal motor neurons following axonal crush and cut. In control conditions, motor neurons were devoid of pro-TGFα immunoreactivity. In the mutant lumbar spinal cord, pro-TGFα immunoreactive motor neurons appeared as soon as the disease developed and pro-TGFα expression persisted until the latest stages of degeneration. Motor neurons and astrocytes of the white matter weakly immunoreactive for the TGFα receptor were also present in both control and mutant lumbar spinal cords. Following hypoglossal nerve crush and cut, motoneuronal pro-TGFα expression was precocious and transient, visible at one day post-injury and lasting for only 3 days, during which time astrocyte-like cells immunoreactive for both TGFα and its receptor appeared within the injured nucleus. Enhanced TGFα mRNA levels following nerve crush showed that activation occurred at the transcriptional level. These results show that upregulation of TGFα is an early and common response of adult murine motor neurons to injury, regardless of its experimental or genetic origin.