CMT 1 Schwann-cell axon alterations - Research from Rome

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1: Acta Neuropathol (Berl) 2002 Sep;104(3):287-96

Peripheral nerve extracellular matrix remodeling in Charcot-Marie-Tooth

type I disease.

Palumbo C, Massa R, Panico MB, Di Muzio A, Sinibaldi P, Bernardi G,

Modesti A.

Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Universita

di Roma Tor Vergata, Via di Tor Vergata 135, 00133 Rome, Italy.

Charcot-Marie-Tooth type 1 disease (CMT1) is a group of inherited

demyelinating neuropathies caused by mutations in genes expressed by

myelinating Schwann cells. Rather than demyelination per se, alterations

of Schwann cell-axon interactions have been suggested as the main cause

of motor-sensory impairment in CMT1 patients. In an attempt to identify

molecules that may be involved in such altered interactions, the

extracellular matrix (ECM) remodeling occurring in CMT1 sural nerves was

studied. For

comparison, both normal sural nerves and sural nerves affected by

neuropathies of different origin were used. The study was performed by

immunohistochemical analysis using antibodies against collagen types I,

III, IV, V, and VI and the glycoproteins fibronectin, laminin,

vitronectin and tenascin. Up-regulation of collagens, fibronectin and

laminin was commonly found in nerve biopsy specimens from patients

affected by CMT1 and control diseases, but higher levels of

overexpression were usually observed in CMT1 cases. On the other hand,

vitronectin and tenascin appeared preferentially induced in CMT1

compared to other pathologies investigated here.

Vitronectin, whose expression in normal nerves was limited to

perineurial layers and to the walls of epineurial and endoneurial

vessels, became strongly and diffusely expressed in the endoneurium in

most CMT1 biopsy specimens. The expression of tenascin, confined to the

perineurium, to vessel walls and to the nodes of Ranvier in normal

nerves, was displaced and extended along the internodes of several nerve

fibers in the majority of CMT1 nerves. Thus, compared with our

pathological controls CMT1 seemed to determine the most extensive

remodeling of peripheral nerve ECM.