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Imaging of neurotransmission in humnan brains : Normal and abnormal aging.

人脑神经传递成像：正常和异常衰老。

基本信息

批准号：
06833002
负责人：
YANAI Kazuhiko
金额：
$ 1.34万
依托单位：
Tohoku University of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06833002/
关键词：
Histamine Histamine H1 receptor Aging Alzheimer disease PET human brain H3 receptor ヒスタミンH-1受容体ノックアウトマウス

项目摘要

Recently, the histaminergic neuron system in the brain has been clarified and shown to be involved in many physiological functions such as learning. sleep-wakefulness, food intake, drinking, body temperature, neuroendocrine control, and so on. However, there have been few studies on the relationship between the central histaminergic neuron system and aging process. The purpose of our study is to elucidate the role of the central histaminergic neurons in normal and abnormal aging process using multidisciplinary methods from basic and clinical points of view.(1)The central histaminergic neuron system in rodent models of dementia : The effects of histamine H3 receptor antagonists on learning and memory disability. The histaminergic neuron system in senescence-accelerated mice model (SAM) was examined. The activity of histidine decarboxylase (HDC) was decreased in the cortex of SAM.The level of HDC was restored to that of control after the administration of H3 receptor antagonist to SAM.In addition, learning ability was also improved in SAM after the treatment of H3 antagonists.(2)Human PET studies of Alzheimer disease. Histamine H1 receptors in humen brains measured using positron emission tomography (PET) : The effects of normal and abnormal aging on H1 receptors were examined using [^<11>C] doxepin as a probe of histamine H1 receptors. Age-related decrease in [^<11>C] doxepin binding was observed by PET.Furthermore, the binding of [^<11>C] doxepin was markedly decreased in cortical tissues of Alzheimer disease when compared with age-and sex-matched controls.

最近，大脑中的组胺能神经元系统已经被阐明，并被证明参与了许多生理功能，如学习。睡眠-觉醒、食物摄入、饮酒、体温、神经内分泌控制等。然而，关于中枢组胺能神经元系统与衰老过程的关系的研究很少。本研究的目的是从基础和临床的角度用多学科的方法阐明中枢组胺能神经元在正常和异常衰老过程中的作用。(1)痴呆模型中的中枢组胺能神经元系统：组胺H3受体拮抗剂对学习记忆障碍的影响。对加速衰老小鼠模型(SAM)的组胺能神经元系统进行了检测。SAM大鼠大脑皮质HDC活性降低，给予H3受体拮抗剂后，HDC水平恢复至对照组水平，且SAM经H3受体拮抗剂治疗后，学习能力也得到改善。(2)人类阿尔茨海默病的PET研究。正电子发射断层扫描(PET)测定人脑组织中组胺H1受体：以多塞平作为组胺H1受体的探针，观察正常和异常衰老对组胺H1受体的影响。PET观察到[^&lt；11&gt；C]多塞平结合量随年龄增长而降低。此外，与年龄和性别匹配的对照组相比，阿尔茨海默病患者皮质组织中[^&lt；11&gt；C]多塞平结合量显著减少。