Schwann Cells Express Motor and Sensory Phenotypes That Regulate Axon Regeneration

Abstract

Schwann cell phenotype is classified as either myelinating or nonmyelinating. Additional phenotypic specialization is suggested, however, by the preferential reinnervation of muscle pathways by motoneurons. To explore potential differences in growth factor expression between sensory and motor nerve, grafts of cutaneous nerve or ventral root were denervated, reinnervated with cutaneous axons, or reinnervated with motor axons. Competitive reverse transcription-PCR was performed on normal cutaneous nerve and ventral root and on graft preparations 5, 15, and 30 d after surgery. mRNA for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor, hepatocyte growth factor, and insulin-like growth factor-1 was expressed vigorously by denervated and reinnervated cutaneous nerve but minimally by ventral root. In contrast, mRNA for pleiotrophin (PTN) and glial cell line-derived neurotrophic factor was upregulated to a greater degree in ventral root. ELISA confirmed that NGF and BDNF protein were significantly more abundant in denervated cutaneous nerve than in denervated ventral root, but that PTN protein was more abundant in denervated ventral root. The motor phenotype was not immutable and could be modified toward the sensory phenotype by prolonged reinnervation of ventral root by cutaneous axons. Retrograde labeling to quantify regenerating neurons demonstrated that cutaneous nerve preferentially supported cutaneous axon regeneration, whereas ventral root preferentially supported motor axon regeneration. Schwann cells thus express distinct sensory and motor phenotypes that are associated with the support of regeneration in a phenotype-specific manner. These findings suggest that current techniques of bridging gaps in motor and mixed nerve with cutaneous graft could be improved by matching axon and Schwann cell properties.

Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans

“…Examples include the upregulation of neurotrophic factors, galectin-1, and cytoskeletal proteins, including actin and T-α-1 tubulin in the neurons [43][44][45][46], and neurotrophic factors and their receptors in the Schwann cells ( Fig. 3a) [31,41,42,[47][48][49]. A specific example of upregulation of T-α-1 tubulin in the neurons is shown in Fig.…”

“…3). There is a rapid upregulation of neurotrophic factors and their receptors in motoneurons and in Schwann cells, but this upregulation is short-lived, declining to baseline levels within a month or more of chronic axotomy and chronic denervation, respectively [31,[39][40][41][42]. Examples include the upregulation of neurotrophic factors, galectin-1, and cytoskeletal proteins, including actin and T-α-1 tubulin in the neurons [43][44][45][46], and neurotrophic factors and their receptors in the Schwann cells ( Fig.…”

The design of electrospun PLLA nanofiber scaffolds compatible with serum-free growth of primary motor and sensory neurons

“…For example, the nervous system contains highly stereotyped morphologies of neurons in the cerebellum, hippocampus and olfactory bulb [5], as well as over 100 subtypes of neurons in the cerebral cortex alone [6]. Even in peripheral nerve, the simplest system in which to study regeneration, there are both motor and sensory neurons with multiple types of nerve fibers each [7], as well as Schwann cells expressing phenotypes that independently regulate motor and sensory neuron regeneration [8]. Moreover, numerous design parameters for fibrous scaffolds need to be resolved, including the choices of fiber material, diameter and alignment.…”

Misdirection and guidance of regenerating axons after experimental nerve injury and repair

“…In addition, the profile of growth factor expression might differ for Schwann cells inside motor versus sensory nerves. 31 Another factor that might determine successful regeneration of the axon across the basal lamina tube is the interaction of the GC with specific cell adhesion molecules. Examples of such factors are L2 and HNK-1, 43,44 and PSA-NCAM.…”