Pattern of hypocretin (orexin) soma and axon loss, and gliosis, in human narcolepsy.
|Title||Pattern of hypocretin (orexin) soma and axon loss, and gliosis, in human narcolepsy.|
|Publication Type||Journal Article|
|Year of Publication||2003|
|Authors||Thannickal TC, Siegel JM, Nienhuis R, Moore RY|
|Date Published||2003 Jul|
|Keywords||Adult, Aged, Aged, 80 and over, Astrocytes, Axons, Brain Stem, Carrier Proteins, Cell Count, Female, Glial Fibrillary Acidic Protein, Gliosis, Humans, Hypothalamus, Intracellular Signaling Peptides and Proteins, Male, Middle Aged, Narcolepsy, Neurons, Neuropeptides, Orexins|
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 brain-stem 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.
|Alternate Journal||Brain Pathol.|
|Grant List||HL41370 / HL / NHLBI NIH HHS / United States |
MH64109 / MH / NIMH NIH HHS / United States
NS14610 / NS / NINDS NIH HHS / United States