Pattern of Hypocretin (Orexin) Soma and Axon Loss, and Gliosis, in Human Narcolepsy
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.
Từ khóa
Tài liệu tham khảo
Chemelli RM, 2000, Polysomnographic characterization of orexin‐2 receptor knockout mice, Sleep, 23, A296
DeArmond SJ, 1989, Structure of the human brain a photographic atlas
Guilleminault C., 1994, Principles and practice of sleep medicine
Honda Y, 1984, Narcolepsy and HLA: Positive DR2 as a prerequisite for the development of narcolepsy, Folia Psychiatr Neurol Jpn, 38, 360
Howard CV, 1998, Unbiased stereology: three dimensional measurement in microscopy
Kisanuki Y, 2000, The role of orexin receptor type‐1 (OX1R) in the regulation of sleep, Sleep, 23, A91
Lin JS, 1986, Histamine‐immunoreactive neurons in the hypothalamus of cats, C R Acad Sc Paris, 303, 371
Moore RY, 2001, The hypocretin neuron system: an arousal system in the human brain, Arch Ital de Biol, 139, 195
Nishino S, 2002, CSF histamine content is decreased in hypocretin‐deficient human narcolepsy, Sleep, 25, A476
Peever JH, 2002, Excitatory effects of hypocretin in the trigeminal nucleus are reversed by NMDA antagonism, J Neurophysiol
Thannickal TC, 2000, Human narcolepsy is linked to reduced number, size and synaptic bouton density in hypocretin‐2 labeled neurons, Abstr Soc Neurosci, 26, 2061
Thannickal TC, 2000, Preservation of hypocretin neurons in genetically narcoleptic dogs, Sleep, 23, A296
Thannickal TC, 2002, Increased number of astrocytes and reduced density of hypocretin/orexin fibers in human narcolepsy, Sleep, 25A
Wagner D, 2000, Distribution of hypocretin‐containing neurons in the lateral hypothalamus and C‐fos‐immunoreactive neurons in the VLPO, Sleep Res Online, 3, 35