کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6278595 | 1295836 | 2007 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The development of hypocretin (OREXIN) deficiency in hypocretin/ataxin-3 transgenic rats
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کلمات کلیدی
SOREMPHcrtREMTSDRIAataxin - آتاکسینElectroencephalogram - الکتروانسفالوگرافیelectromyogram - الکترومیوگرافیEMG - الکترومیوگرافیanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceTransgenic - تراریختهrapid eye movement - حرکت سریع چشمNarcolepsy - حمله خواب، خوابتازش، نارکولپسیSleep - خوابREM sleep - خواب همراه با حرکات سریع چشمradioimmunoassay - رادیوایمونواسیZeitgeber time - زمان تایمرCSF - مایع مغزی نخاعیCerebrospinal fluid - مایع مغزی نخاعیTotal sleep deprivation - محرومیت از خواب کاملEEG - نوار مغزیwild type - نوع وحشیHypothalamus - هیپوتالاموسlateral hypothalamus - هیپوتالاموس جانبیHypocretin - هیپوکراتین
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
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چکیده انگلیسی
Narcolepsy is linked to a widespread loss of neurons containing the neuropeptide hypocretin (HCRT), also named orexin. A transgenic (TG) rat model has been developed to mimic the neuronal loss found in narcoleptic humans. In these rats, HCRT neurons gradually die as a result of the expression of a poly-glutamine repeat under the control of the HCRT promoter. To better characterize the changes in HCRT-1 levels in response to the gradual HCRT neuronal loss cerebrospinal fluid (CSF) HCRT-1 levels were measured in various age groups (2-82 weeks) of wild-type (WT) and TG Sprague-Dawley rats. TG rats showed a sharp decline in CSF HCRT-1 level at week 4 with levels remaining consistently low (26%±9%, mean±S.D.) thereafter compared with WT rats. In TG rats, HCRT-1 levels were dramatically lower in target regions such as the cortex and brainstem (100-fold), indicating decreased HCRT-1 levels at terminals. In TG rats, CSF HCRT-1 levels significantly increased in response to 6 h of prolonged waking, indicating that the remaining HCRT neurons can be stimulated to release more neuropeptide. Rapid eye movement (REM) sleep in TG rats (n=5) was consistent with a HCRT deficiency. In TG rats HCRT immunoreactive (HCRT-ir) neurons were present in the lateral hypothalamus (LH), even in old rats (24 months) but some HCRT-ir somata were in various stages of disintegration. The low output of these neurons is consistent with a widespread dysfunction of these neurons, and establishes this model as a tool to investigate the consequences of partial hypocretin deficiency.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 148, Issue 1, 10 August 2007, Pages 34-43
Journal: Neuroscience - Volume 148, Issue 1, 10 August 2007, Pages 34-43
نویسندگان
S. Zhang, L. Lin, S. Kaur, S. Thankachan, C. Blanco-Centurion, M. Yanagisawa, E. Mignot, P.J. Shiromani,