CMT 1A DRG cultures model suggest neuroprotective therapies

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Eur J Neurosci. 2006 Mar;23(6):1445-52.

Axonal damage and demyelination in long-term dorsal root ganglia

cultures from a rat model of Charcot-Marie-Tooth type 1A disease.

Nobbio L, Gherardi G, Vigo T, Passalacqua M, Melloni E, Abbruzzese M,

Mancardi G, Nave KA, Schenone A.

Department of Neurosciences, Ophthalmology and Genetics, University

of Genoa, Italy, Via De Toni, 5, 16132, Genoa, Italy.

Clinical progression in hereditary and acquired demyelinating

disorders of both the central and peripheral nervous system is mainly

due to a time-dependent axonal impairment. We established 90-day

dorsal root ganglia (DRG) cultures from a rat model of Charcot-Marie-

Tooth type 1A (CMT1A) neuropathy to evaluate the structure of myelin

and axons, and the expression of myelin-related proteins and

cytoskeletal components, by morphological and molecular techniques.

Both wild-type and CMT1A cultures were rich in myelinated fibres.

Affected cultures showed dysmyelinated internodes and focal myelin

swellings. Furthermore, uncompacted myelin and smaller axons with

increased neurofilament (NF) density were found by electron

microscopy, and Western blots showed higher levels of

nonphosphorylated NF.

Confocal microscopy demonstrated an abnormal distribution of the

myelin-associated glycoprotein which, instead of being expressed at

the noncompact myelin level, showed focal accumulation along the

internodes while other myelin proteins were normally distributed.

These findings suggest that CMT1A DRG cultures, similarly to the

animal model and human disease, undergo axonal atrophy over a period

of time. This model may be utilized to study the molecular changes

underlying demyelination and secondary axonal impairment. As axonal

damage may occur after just 3 months and tissue cultures represent a

strictly controlled environment, this model may be ideal for testing

neuroprotective therapies.