Retrograde axonal transport of ciliary neurotrophic factor is increased by peripheral nerve injury

Abstract

Ciliary neurotrophic factor (CNTF) promotes the survival of several populations of neurons, including sensory and motor neurons. Although CNTF is abundant in adult sciatic nerve, the mature protein lacks a signal sequence and is not secreted; therefore, it has been proposed to act as a lesion factor. The identification of a functional CNTF receptor revealed ligand-specific phosphorylation cascades and gene induction. However, it is not clear how these signal-transducing events are elicited in neuronal cell bodies that may be distant from the source of CNTF. We report here that CNTF can be retrogradely transported by adult sensory neurons. More importantly, sensory and motor neurons both show greatly increased transport of CNTF following peripheral nerve lesion. Axotomy-induced increases in retrograde transport of neurotrophic factors may be an important response of neuronal cell bodies during regeneration.

Prevention of sensory disorders in diabetic Sprague-Dawley rats by aldose reductase inhibition or treatment with ciliary neurotrophic factor

“…This distinguishes CNTF from members of the neurotrophin family of neurotrophic factors, which either have no effect on thermal discrimination in diabetes (as we found using BDNF with a dose that protects large fibres from hyperglycaemia [21]), or have hyperalgesic effects on control and diabetic animals, as reported for nerve growth factor [5]. CNTF has been largely associated with peripheral motor and sensory neuron survival and regeneration after injury [37,38], rather than with the provision of ongoing neurotrophic support in the adult nervous system. Nevertheless, the CNTFRα receptor for CNTF is expressed by both large and small cell bodies in adult sensory ganglia and is detected in peripheral nerve axons [39].…”

Dynamic ubiquitination drives herpesvirus neuroinvasion

“…Of those that do, neuroinvasion is infrequent (i.e., poliovirus, measles virus, mumps virus, West Nile virus, Japanese encephalitic virus, and Chandipura virus) or occurs following an animal bite (i.e., rabies virus). In the case of the latter, mechanical tissue disruption at the site of inoculation bypasses intrinsic protective barriers in the skin and increases retrograde transport in damaged axons as part of a peripheral nerve repair response (36,37). The concept that tissue trauma can increase the susceptibility of the nervous system to neurotropic viruses is best documented for poliovirus, which is rarely neuroinvasive except when provoked by tissue injury (38)(39)(40).…”

Neurotrophins: Potential Therapeutic Tools for the Treatment of Spinal Cord Injury

“…Transplantation of Schwann cells into sites of CNS injury, including the lesioned spinal cord, mimics the effects of peripheral nerve grafts and supports axonal regeneration [42,43]. In addition to potentially myelinating regenerated axons, Schwann cells express cell adhesion molecules, produce components of the extracellular matrix, and secrete multiple neurotrophic factors [44][45][46][47][48][49][50][51][52][53]. Whether grafted Schwann cells provide an advantage in comparision with other potential cell grafts remains to be determined; however, as the grafted cells survive poorly in the lesioned spinal cord, they are soon replaced by migrating endogenous Schwann cells [54,55].…”

“…Sciatic lesion in neonatal mice results in a loss of approximately two-thirds of the lower motor neurons in the lumbar enlargement, which is completely ameliorated with the application of BDNF, NT-3, or insulin-like growth factor I (IGF-I) [78]. This death of neonatal motor neurons is in stark contrast to lower motor neurons that not only survive, but regenerate following adult sciatic nerve injury; sciatic injury has been shown to result in increased NGF, BDNF, IGFs, cilliary neurotrophic factor, and glial-derived neurotrophic factor secretion from Schwann cells [44][45][46][47][48][49][50][51][52][53]. Antibody depletion of Schwann cell-produced BDNF leads to decreased regeneration and deficits in myelination of lower motor neurons and sensory neurons [79][80][81].…”