Axonal damage and demyelination in long-term dorsal root ganglia cultures from a rat model of Charcot-Marie-Tooth type 1A disease

摘要: Clinical progression in hereditary and acquired demyelinating disorders of both the central peripheral nervous system is mainly due to a time-dependent axonal impairment. We established 90-day dorsal root ganglia (DRG) cultures from rat model Charcot-Marie-Tooth type 1A (CMT1A) neuropathy evaluate structure myelin axons, expression myelin-related proteins cytoskeletal components, by morphological molecular techniques. Both wild-type CMT1A were rich myelinated fibres. Affected showed dysmyelinated internodes focal swellings. Furthermore, uncompacted smaller axons with increased neurofilament (NF) density found electron microscopy, Western blots higher levels nonphosphorylated NF. Confocal microscopy demonstrated an abnormal distribution myelin-associated glycoprotein which, instead being expressed at noncompact level, accumulation along while other normally distributed. These findings suggest that DRG cultures, similarly animal human disease, undergo atrophy over period time. This may be utilized study changes underlying demyelination secondary As damage occur after just 3 months tissue represent strictly controlled environment, this ideal for testing neuroprotective therapies.