2005 Fiscal Year Final Research Report Summary
Neural mechanisms of cognitive dysfunction caused by sleep deprivation : a study of PET with macaque monkeys.
| Project/Area Number |
16614016
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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 |
睡眠学
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| Research Institution | Tokyo Metropolitan Organization for Medical Research |
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Principal Investigator |
ONOE Hirotaka Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Newroscience Department of Psychology, Senior Researcher, 東京都神経科学総合研究所, 主任研究員 (80214196)
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| Co-Investigator(Kenkyū-buntansha) |
KODAMA Tohru Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Newroscience Department of Psychology, Staff Scientist, 副参事研究員 (20195746)
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| Project Period (FY) |
2004 – 2005
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| Keywords | sleep deprivation / visual disctimination / macaque monkey / fatigue / higher brain function / limbic system / GABAergic neuron / thalamus |
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| Research Abstract |
In order to assess the role of GABAergic neurotransmission in fatigue caused by sleep deficit, we examined the effects of one-night sleep deprivation (SD) on the brain GABA_A receptor binding using the positron emission tomography (PET) with macaque monkeys. The monkeys (macaca mulatta) were trained in a continuous simple visual reaction task (CSVRT), which is required to repeat a visual-guided lever pressing, until they had been skillful in performing the task by a long-term training. The reaction time (RT) which is required for responding to the visual cue and for repeating tasks was measured to estimate the behavioral performance affected by SD. To measure the binding activity of the GABA_A receptor, two ^<11>C-labeled benzodiazepine analogues, [^<11>C]Ro15-4513 and [^<11>C]Ro15-1788, were used in the PET study. Parametric images of the binding potential (BP) was generated by a simplified reference tissue model (SRTM) based on pixel-wise kinetic modeling (PMOD) using a time activity curve of the pons as a reference. Statistical analysis of the resultant images was performed using SPM99 software. The reaction time for CSVRT was significantly prolonged by the SD. The binding activities of [^<11>C]Ro15-4513 but not [^<11>C]Ro15-1788 in the limbic structures such as the anterior cingulate and amygdala were significantly increased by SD. In addition, binding activity of the thalamus was significantly correlated with the. delay of RT. These behavioral and PET imaging results strongly indicate that the increase in the central fatigue caused by SD might be associated with the activation of GABAergic neurotransmission in the limbic structure through presumably alpha 5 subunit containing GABA_A receptor.
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