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Histamine and learning-memory and convulsion

组胺与学习记忆和惊厥

基本信息

批准号：
05454663
负责人：
WATANABE Takehiko
金额：
$ 4.35万
依托单位：
Tohoku University Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454663/
关键词：
Histamine Learning-Memory Convulsion PET Aging

项目摘要

Our major findings of the studies are as follows.(1) When the histaminergic neuron system is activated pharmacologically, the duration periods of electroconvulsion are shortened. On the other hand, when the neuron is inactivated, the duration periods are prolonged. Thus, histamine is anticonvulsant.(2) The threshold of electroconvulsion is lower in young mice (3 weeks) than in adult mice (>6 weeks), and the value is decreased further by an H1 antagonist, pyrilamine, but not by terfenadine, a non-sedative antihistaminic. These findings are consistnet with our clinical observation that the symptoms of some patients of epilepsy became worse when ketotifen was prescribed for allergic diseases, but they are well controlled when terfenadine was used.(3) Thioperamide, an H3 antagonist, shoretend the latency in passive avoidance test of senescence accelerated mice. When the brain histamine level was decreased by treatment with an inhibitor of histidine decarboxylase, the death of neural cells … More in CA 2 region of the hippocampus of gerbils subjected to ischemia by a transient occlusion of the carotid arteries was promoted compared to control group. These findings suggest that the histaminergic system is involved in learning and memory processes.(4) The double label autoradiography of a brain section was developed by taking advantage of the difference in the half-lives of 3H and 11C.The application of the method showed that H3 receptros are modulated by dopaminergic neurons through D1 receptors.(5) The distribution of H1 receptors in the living human brain was mapped by PET with [11C] doxepin as a tracer. Its density decreased by aging in the ratio of 13 % per a decade. The density was higher in the foci of abnormal discharge of patients with complex partial seizure than in the opposite side, showing that the H1 receptors are up-regulated in the foci. The observation is in good agreement with the idea that brain histamine is anticonvulsant, which was obtained by pharmacological studies described above. The density was significantly lower in the cerebral cortices of patients of Alzheimer'disease or multiinfarct dementia than the age- and sex-matched normal controls. Less

我们的主要研究结果如下。(1)当组胺能神经元系统被激活时，电惊厥的持续时间缩短。另一方面，当神经元失活时，持续时间延长。因此，组胺是抗惊厥药。(2)年轻小鼠（3周）的电惊厥阈值低于成年小鼠（>6周），H1拮抗剂吡拉明可进一步降低该值，但非镇静抗组胺药特非那定不会降低该值。这些结果与我们的临床观察相一致，即有些癫痫患者在服用酮替芬治疗过敏性疾病时症状加重，而服用特非那定后症状得到很好的控制。(3)H_3受体拮抗剂硫哌丁胺可缩短快速老化小鼠被动回避反应的潜伏期。当用组氨酸脱羧酶抑制剂降低脑组织组胺水平时， ...更多信息与对照组相比，沙土鼠颈动脉短暂闭塞引起的海马CA 2区的神经元数量增加。这些发现表明，组胺能系统参与学习和记忆过程。(4)利用~ 3 H和~（11）C半衰期的差异，建立了脑切片的双标记放射自显影方法，证明多巴胺能神经元通过D_1受体调节H_3受体。(5)以[11 C]多塞平为示踪剂，用PET法对H1受体在活体人脑中的分布进行了定位。其密度随老化以每10年13%的比例下降.复杂部分性发作患者异常放电灶内的密度高于对侧，表明病灶内H1受体表达上调。该观察结果与通过上述药理学研究获得的脑组胺是抗惊厥剂的观点非常一致。与年龄和性别匹配的正常对照组相比，阿尔茨海默病或多梗死性痴呆患者的大脑皮质中的密度显着降低。少