Schwann cells express motor and sensory phenotypes that regulate axon regenerati

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J Neurosci. 2006 Sep 20;26(38):9646-55.

Schwann cells express motor and sensory phenotypes that regulate

axon regeneration.

Hoke A, Redett R, Hameed H, Jari R, Zhou C, Li ZB, JW,

Brushart TM.

Department of Orthopaedics, s Hopkins University School of

Medicine, Baltimore, land 21287, USA.

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.