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Volume 16, Number 15, Issue of August 1, 1996 pp. 4588-4595
Copyright ©1996 Society for Neuroscience

Major Histocompatibility Class II Molecules in the CNS: Increased Microglial Expression at the Onset of Narcolepsy in a Canine Model

Received March 11, 1996; revised April 29, 1996; accepted May 10, 1996.

Mehdi Tafti¹, Seiji Nishino¹, Michael S. Aldrich², Wennie Liao¹, William C. Dement¹, and Emmanuel Mignot¹

¹ Sleep Disorders Center, Department of Psychiatry, Stanford University, Palo Alto, California 94304, and ² Department of Neurology, University of Michigan, Ann Arbor, Michigan 48109

Human narcolepsy is a neurological disorder known to be closely associated with HLA-DR2 and DQB1*0602. Because most autoimmune diseases are HLA-associated, a similar mechanism has been proposed for narcolepsy. However, neither systemic nor CNS evidence of an autoimmune abnormality 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 significant increase of MHC class II expression by the microglia. Moreover, the highest values were found between 3 and 8 months of age, strikingly concomitant to the development of narcolepsy in the canine model. In humans, class II expression was not found significantly different between 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 in narcoleptics and controls, respectively), because class II expression is significantly correlated with age in both humans and dogs. For the first time, this study demonstrated that the expression of MHC class II molecules in the CNS is age-dependent and that a consistent increase of their expression by the microglia might be critically involved in the development of narcolepsy.

Key words: narcolepsy; MHC class II; microglia; development; gene expression; immunohistochemistry; Northern analysis

This article has been cited by other articles:

				J. M. Siegel, R. Nienhuis, S. Gulyani, S. Ouyang, M. F. Wu, E. Mignot, R. C. Switzer, G. McMurry, and M. Cornford Neuronal Degeneration in Canine Narcolepsy J. Neurosci., January 1, 1999; 19(1): 248 - 257. [Abstract] [Full Text] [PDF]

				H. Kadotani, J. Faraco, and E. Mignot Genetic Studies in the Sleep Disorder Narcolepsy Genome Res., May 1, 1998; 8(5): 427 - 434. [Abstract] [Full Text]

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