| Project/Area Number |
21591500
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Akita University |
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Principal Investigator |
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | ナルコレプシー / オレキシン / 2次性過眠症 / 脳内鉄代謝 / むずむず脚症候群 / ナルコヒプシー |
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| Research Abstract |
(1) Narcolepsy occurs during the course of various neurological conditions. A recent meta-analysis indicated that 10 out of 116 symptomatic cases of narcolepsy are associated with multiple sclerosis, a disease of autoimmune demyelination. Symptomatic narcoleptic cases consist of heterogeneous disease conditions, but the orexin systems are often impaired in these narcolepsy/EDS cases. Since, serum anti.aquaporin 4 (AQP4=NMO) antibody titer were positive, seven Japanese patients were diagnosed as neuromyelitis optica (NMO) related disorder. Bilateral and symmetrical hypothalamic lesions associated with marked or moderate orexin deficiency were found in all 7 cases. Four of these patients met the ICSD 2 narcolepsy criteria. Since AQP4 is highly expressed in the hypothalamic periventricular regions, an immune attack on AQP4 may be partially responsible for the bilateral and hypothalamic lesions and orexin deficiency in narcolepsy/EDS associated with autoimmune demyelinating diseases. Gaini
… More
ng the basic knowledge of symptomatic narcolepsy in immune mediated conditions will not be useful only for selecting the most appropriate treatment and predicting the prognosis of the disease but also for understanding the etiological mechanism of narcolepsy.
(2) Periodic leg movements during sleep (PLMS) are often associated with restless legs syndrome (RLS). Reduced ferritin and elevated transferrin levels (with normal or low iron levels) in CSF (as indicators of low brain iron) are reported in PLMS/RLS subjects. A much higher incidence (25-50% vs.-5% in general population) of PLMS is reported in narcoleptic patients. Since altered dopaminergic neurotransmissions are suggested in both diseases and since iron is a co-factor for dopamine synthesis (thyrosine hydoroxylase), we evaluated CSF ferritin, transferrin and iron in patients with orexin deficient narcolepsy in the study. Patients with orexin deficient narcolepsy had higher CSF transferrin and iron levels compared to control subjects. There was no difference in CSF ferritin levels between the two groups. As seen in RLS subjects, an increase in transferrin was observed in narcoleptic subjects. However, normal ferritin and increased iron levels in these subjects may possibly suggest a higher utilization of iron or a dysregulation of iron metabolites in narcolepsy. It is not known if these findings are direct or indirect (such as a compensatory increase in dopaminergic synthesis) to orexin deficiency, and whether or not this contributes to the high incidence of PLMS in narcolepsy. Less
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