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

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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.