Re-expression of Nerve Growth Factor Receptor after Axonal Injury Recapitulates a Developmental Event in Motor Neurons: Differential Regulation when Regeneration is Allowed or Prevented

Abstract

Motor neurons in the brainstem and spinal cord transiently express nerve growth factor receptors (NGFr) during development, but not in normal adult animals. In this study, NGFr was immunohistochemically identified in hypoglossal motor neurons after different types of peripheral axonal injury in adult rats. NGFr is re-expressed in motor neurons 7 days after a nerve crush injury, and has disappeared again by 28 days. These times correspond, respectively, to the active phase of regeneration, and a time by which regeneration has largely been completed, as determined by electrical activation of tongue muscle twitch. In contrast, 7 days after nerve transection and ligation of the proximal stump to prevent regeneration, there is no re-expression of NGFr, but 28 days after such treatment NGFr is present in a few neurons. By this time, neuroma formation has begun proximal to the end of the cut and ligated nerve. Together, these findings suggest that motor neurons transiently re-express NGFr during regeneration and not in response to axonal transection per se. The signal triggering re-expression thus seems more likely to be the introduction of a message from the site of injury, rather than the loss of a target-derived message. Although the function of NGFr in developing and regenerating motor neurons is not known, its expression appears to be associated with periods of axonal growth and maturation.