MAJOR HISTOCOMPATIBILITY CLASS-II MOLECULES IN THE CNS - INCREASED MICROGLIAL EXPRESSION AT THE ONSET OF NARCOLEPSY IN A CANINE MODEL

Human narcolepsy is a neurological disorder known to be closely associ ated with HLA-DR2 and DQB10602. Because most autoimmune diseases are HLA-associated, a similar mechanism has been proposed for narcolepsy. However, neither systemic nor CNS evidence of an autoimmune abnormalit y has ever been reported. In this study, major histocompatibility (MHC ) class I and class II expression was studied in the CNS of human and canine narcoleptics using immunohistochemistry and Northern analysis. Results indicate that canine narcolepsy is associated with a significa nt increase of MHC class II expression by the microglia. Moreover, the highest values were found between 3 and 8 months of age, strikingly c oncomitant to the development of narcolepsy in the canine model. In hu mans, class II expression was not found significantly different betwee n control and narcoleptic subjects. This result could be explained by the old age of the subjects (69.86 +/- 5.31 and 68.36 +/- 4.74 years i n narcoleptics and controls, respectively), because class II expressio n is significantly correlated with age in both humans and dogs. For th e first time, this study demonstrated that the expression of MHC class II molecules in the CNS is age-dependent and that a consistent increa se of their expression by the microglia might be critically involved i n the development of narcolepsy.