Abstract
Neurotrophins are a family of proteins that regulate neuronal survival, synaptic function, and neurotransmitter release, and elicit the plasticity and growth of axons within the adult central and peripheral nervous system. Since the 1950s, these factors have been extensively studied in traumatic injury models. Here we review several members of the classical family of neurotrophins, the receptors they bind to, and their contribution to axonal regeneration and sprouting of sensory and motor pathways after spinal cord injury (SCI). We focus on nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and their effects on populations of neurons within diverse spinal tracts. Understanding the cellular targets of neurotrophins and the responsiveness of specific neuronal populations will allow for the most efficient treatment strategies in the injured spinal cord.
Highlights
In the adult central nervous system, axons fail to regenerate after injury
These factors contribute to neuronal survival, axonal plasticity, and synaptic function, including neurotransmitter availability [1,2,3,4,5,6,7,8,9]
The combination of other neurotrophins such as brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5), or guidance molecules such as semaphorins, with nerve growth factor (NGF) expression alter sprouting of primary sensory pathways in vivo [78,79,80,81,82]
Summary
In the adult central nervous system, axons fail to regenerate after injury. This lack of regeneration can be attributed to diminished activation of intrinsic growth programs, and a local environment that both lacks growth permissive molecules and contains many growth inhibitory molecules. Pro-NGF, which is the most well-defined proneurotrophin, has been implicated in the death of oligodendrocytes, spinal motor neurons, and corticospinal neurons in a p75NTR dependent manner [36,37,38] Upregulation of this molecule can occur in the injured state [12,13,14]. The combination of other neurotrophins such as brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5), or guidance molecules such as semaphorins, with NGF expression alter sprouting of primary sensory pathways in vivo [78,79,80,81,82] These studies demonstrate improved axonal growth and some functional recovery of nociception [80,81,82] or hindlimb motor function [78,79] in models of spinal cord injury. Other treatment options may include modulating the cleavage of pro-forms to encourage the presence of more mature neurotrophins
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