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，已经澄清了大脑中的组胺能神经元系统，并证明与许多生理功能有关。睡眠吸收，食物摄入量，饮酒，体温，神经内分泌控制等。但是，关于中央组胺能神经元系统与衰老过程之间关系的研究很少。我们研究的目的是使用从基本和临床观点的多学科方法来阐明中央组蛋白能神经元在正常和异常老化过程中的作用。检查了衰老加速小鼠模型（SAM）中的组胺能神经元系统。在SAM的皮层中，组氨酸脱羧酶（HDC）的活性降低。HDC的水平在给予H3受体拮抗剂为SAM的情况下恢复为对照的水平。在H3拮抗剂治疗后，SAM的学习能力也提高了H3拮抗剂的学习能力。使用正电子发射断层扫描（PET）测量的Humen大脑中的组胺H1受体：使用[^<11> C] Doxepin作为组胺H1受体的探测，对正常和异常衰老对H1受体的影响进行了检查。在[^<11> c] doxepin结合的[^<11> c] doxepin结合的情况下，[^<11> c] doxepin的结合在阿尔茨海默氏病皮质组织中显着降低，而与年龄和性别匹配的对照组相比。