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

近年来，大脑中的组胺能神经元系统已被阐明，并被证明参与许多生理功能，如学习。睡眠、觉醒、饮食、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之间关系的研究很少。本研究的目的是通过多学科的方法从基础和临床的角度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)痴呆啮齿动物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。对衰老加速小鼠模型（SAM）的组胺能神经元系统进行了检测。SAM皮层组氨酸脱羧酶（HDC）活性降低。在给予SAM H3受体拮抗剂后，HDC水平恢复到对照组水平。此外，在H3拮抗剂治疗后，SAM的学习能力也有所提高。(2)阿尔茨海默病的人体PET研究。正电子发射断层扫描（PET）测定人脑组胺H1受体：用[^<11 b> C]多塞平作为组胺H1受体探针，研究正常和异常衰老对H1受体的影响。PET观察到doxepin结合[^<11 bb0 C]的年龄相关性下降。此外，与年龄和性别匹配的对照组相比，阿尔茨海默病皮质组织中[^<11 bb0 C]多虑平的结合明显减少。

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.