Neurotrophic factors in development and plasticity of spinal neurons

Abstract

Factors affecting neuronal growth may be considered to fall into two major categories: those required for neuronal survival during development or following a lesion, and those which enhance growth or regeneration of axonal or dendritic processes. We briefly review here some recent studies on the former in spinal cord development and plasticity as an introduction to other papers in the session on Factors controlling Neural Growth, and then present in more detail work on factors affecting motoneuron development in vitro. The neurotrophins are a closely-related family of basic neurotrophic factors including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and neurotrophins -3, -4 and -5 that enhance neuronal survival by binding to surface receptors whose major components are the trk tyrosine kinases and p75^NGF-R. Only the latter has been studied in the context of spinal cord neuroplasticity: its levels on motoneurons are up-regulated following central or peripheral trauma, although its function there remains unknown. Much evidence exists for the existence of ‘motoneuron growth factors’ involved in regulation of survival and development of spinal motoneurons. Following a critical comparison of techniques for their purification, we review results obtained in vitro and in vivo using known growth factors such as ciliary neurotrophic factor (CNTF), basic fibroblast growth factor (bFGF) and transforming growth factor (TGF/β1). Although none of them satisfies all the criteria for the embryonic ‘motoneuron growth factor’, CNTF is of potential interest for reducing motoneuron loss in pathological situations.