CMT1 research from biopsies

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© Springer-Verlag 2002

Regular Paper

Peripheral nerve extracellular matrix remodeling in Charcot-Marie-Tooth

type I disease

Camilla Palumbo1, o Massa2, 3, , Beatrice Panico2,

Di Muzio4, Paola Sinibaldi1, Giorgio Bernardi2, 3 and Modesti1

(1)

Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Universita

di Roma Tor Vergata, Rome, Italy

(2)

Dipartimento di Neuroscienze, Universita di Roma Tor Vergata, Via di Tor

Vergata 135, 00133 Rome, Italy

(3)

IRCCS S. Lucia, Rome, Italy

(4)

Centro Regionale Malattie Neuromuscolari, Ospedale

Clinicizzato, Chieti, Italy

The first two authors contributed equally to this study

Abstract.

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.