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|
Human narcolepsy is correlated with a greatly reduced number of hypocretin (orexin) containing neurons and axons, and an elevated level of hypo- thalamic 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 nar- coleptics are not correlated with regional hypocretin cell soma density in normals or with regional percent soma loss in narcoleptics. Rather they are inde- pendently 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 mediat- ed 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.