Pattern of Hypocretin (Orexin) Soma and Axon Loss, and Gliosis, in Human Narcolepsy

Brain Pathology - Tập 13 Số 3 - Trang 340-351 - 2003
Thomas C. Thannickal1,2, Jerome M. Siegel1,2, Robert Nienhuis2, Robert Y. Moore3
1Authors contributed equally to this work
2Department of Psychiatry and Brain Research Institute, University of California, Los Angeles and Neurobiology Research, VA Greater Los Angeles Healthcare System, North Hills, Calif.
3Department of Neurology, University of Pittsburgh, Pa.

Tóm tắt

Human narcolepsy is correlated with a greatly reduced number of hypocretin (orexin) containing neurons and axons, and an elevated level of hypothalamic gliosis. We now report that the percentage loss of Hcrt cells and percentage elevation of GFAP staining are variable across forebrain and brainstem nuclei, and are maximal in the posterior and tuberomammillary hypothalamic region. Regional gliosis and percent loss of hypocretin axons in narcoleptics are not correlated with regional hypocretin cell soma density in normals or with regional percent soma loss in narcoleptics. Rather they are independently and strongly correlated with the regional density of hypocretin axons and the message density for hypocretin receptor 2, as quantified in the rat. These results are consistent with the hypotheses that the loss of hypocretin function in narcolepsy results from a cytotoxic or immunologically mediated attack focused on hypocretin receptor 2 or an antigen anatomically linked to hypocretin receptor 2, and that this process is intensified in regions of high axonal density.

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Brain Pathology

Tập 13 Số 3

340-351

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