PET study of 5-HT1A and GABA receptors in temporal lobe epilepsy.

颞叶癫痫中 5-HT1A 和 GABA 受体的 PET 研究。

• 批准号: 13670988
• 负责人: OKUBO Yoshiro
• 金额: $ 2.24万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670988/
• 关键词: Epilepsy; PET; Serotonin; GABA

It has been demonstrated that serotonin inhibits epileptiform discharge by activation of 5-HT1A receptors in CA1 pyramidal neurons. Further, inhibitory role of 5-HT1A receptor for the development of amygdaloid kindling in rats has been known. In spite of possible involvements of serotoriergic activities, there have been few studies to investigate central serotonergic system in epilepsy, since suitable ligands have been limited. Using a new radioligand, [11C]WAY 100635 for 5-HT1A receptors, we investigated 5-HT1A receptors in patients with temporal lobe epilepsy and healthy controls. Parametric images of binding potential(BP) were made using the reference tissue model, and were analyzed using SPM99. We found marked decrease of 5-HT1A receptor binding in the temporal lobe ipsilateral to EEG foci. But decreased binding was also observed in the contra lateral temporal lobe. Decreased area of 5-HT1A binding was more restricted compared with that of GABA/benzodiazepine receptor which was measured using [11C]frumazenil. Deceresed 5-HT1A binding in the cortex may reflect decreased inhibitory role of 5-HT1A receptor in patients with temporal lobe epilepsy. The present findings suggest that neuroreceptor imaging techniques with [11C]WAY 100635 may give rise to new perspectives for understanding the pathophysiology of epilepsy.

已经证明，5-羟色胺通过激活CA 1锥体神经元中的5-HT 1A受体来抑制癫痫样放电。此外，已知5-HT 1A受体对大鼠杏仁核点燃发展的抑制作用。尽管癫痫可能涉及多巴胺能活动，但由于合适的配体有限，因此对癫痫中枢多巴胺能系统的研究很少。我们使用一种新的5-HT 1A受体放射性配体[11 C]WAY 100635，研究了颞叶癫痫患者和健康对照者的5-HT 1A受体。使用参考组织模型制作结合电位（BP）的参数图像，并使用SPM 99进行分析。我们发现，5-HT 1A受体结合在颞叶EEG病灶同侧显着减少。但在对侧颞叶也观察到结合减少。与使用[11 C]氟马西尼测量的GABA/苯二氮卓类受体相比，5-HT 1A结合面积减少更受限制。颞叶癫痫患者大脑皮层5-HT 1A结合减少可能反映了5-HT 1A受体抑制作用的降低。目前的研究结果表明，[11 C]WAY 100635的神经受体成像技术可能会为理解癫痫的病理生理学带来新的视角。

项目成果

Yasuno F, Suhara T, Okubo Y, Sudo Y, Inoue M, et al.: "Dose relationship of limbic-cortical D 2-dopamine receptor occupancy with risperidone"Psychopharmacology. 154. 112-114 (2001)

Yasuno F、Suhara T、Okubo Y、Sudo Y、Inoue M 等：“边缘皮质 D 2-多巴胺受体占用与利培酮的剂量关系”精神药理学。

Nakayama T, Suhara T, Okubo Y, et al.: "In vivo drug action of tandospirone at 5-HT1A receptor examined with PET and neuroendocrine response"Psychopharmacology. 165. 37-42 (2003)

Nakayama T、Suhara T、Okubo Y 等人：“用 PET 和神经内分泌反应检查坦度螺酮对 5-HT1A 受体的体内药物作用”精神药理学。

大久保善朗, 本間伊佐子: "脳波. 臨床検査学講座生理機能検査学"医歯薬出版. 107-176 (2002)

大久保义郎、本间勇子：“脑电图。临床实验室课程生理功能测试”石药出版 107-176 (2002)。

Oda K, Okubo Y, et al.: "Regional cerebral blood flow in depressed patients with MRI white matter hyperintensity"Biol Psychiatry. 53(2). 150-156 (2003)

Oda K、Okubo Y 等人：“MRI 白质高信号抑郁症患者的区域脑血流”Biol Psychiatry。

Ichimiya T, Okubo Y, Suhara T, Sudo y.: "Reduced Volume of the Cerebellar Vermis in Neuroleptic-Naive Schizophernia"Biological Psychiatry. 49. 20-27 (2001)

Ichimiya T、Okubo Y、Suhara T、Sudo y.：“抗精神病药初治型精神分裂症中小脑蚓部体积减少”生物精神病学。