The Journal of Neuroscience, January 1, 1999, 19(1):248-257

Neuronal Degeneration in Canine Narcolepsy

¹  Veterans Administration Medical Center Sepulveda and Department of Psychiatry and Brain Research Institute, University of California Los Angeles School of Medicine, Neurobiology Research 151A3, Sepulveda, California 91343, ² Department of Psychiatry and Behavioral Sciences, Sleep Research Center, Richard Lucas/Lab Surge Building, Palo Alto, California 94304, ³ NeuroScience Associates, Knoxville, Tennessee 37922, and ⁴ Department of Pathology, Harbor University of California Los Angeles Medical Center, Torrance, California 90509

Narcolepsy is a lifelong illness characterized by persistent sleepiness, hypnagogic hallucinations, and episodes of motor paralysis called cataplexy. We have tested the hypothesis that a transient neurodegenerative process is linked to symptom onset. Using the amino-cupric silver stain on brain sections from canine narcoleptics, we found elevated levels of axonal degeneration in the amygdala, basal forebrain (including the nucleus of the diagonal band, substantia innominata, and preoptic region), entopeduncular nucleus, and medial septal region. Reactive neuronal somata, an indicator of neuronal pathology, were found in the ventral amygdala. Axonal degeneration was maximal at 2-4 months of age. The number of reactive cells was maximal at 1 month of age. These degenerative changes precede or coincide with symptom onset. The forebrain degeneration that we have observed can explain the major symptoms of narcolepsy.

Key words: narcolepsy; REM sleep; amygdala; basal forebrain; canine; amino-cupric silver; degeneration; cataplexy