Evaluation for CSF histamine levels in many disorders and measurements of hypothalamic neuropeptides in the patients with Kleine-Levin syndrome

多种疾病中脑脊液组胺水平的评估以及克莱-莱文综合征患者下丘脑神经肽的测量

• 批准号: 21591501
• 负责人: SHIMIZU Tetsuo
• 金额: $ 3万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591501/
• 关键词: 過眠症; ヒスタミン; オレキシン; Kleine-Levin症候群; Agrp; MCH; AgRP

(1) We first reported that histamine decreases in the primary CNS hypersomnia, such as narcolepsy and idiopathic hypersomnia (Kanbayashi 2009). However, the histamine levels in other diseases are still unknown. We have further estimated the histamine in CSF of several neurological diseases. Histaminergic neurons are located exclusively in the tuberomammillary nucleus (TMN) of the posterior hypothalamus and project their axons to various brain regions. Histamine is released in the brain not only from TMN histamine neurons, but also from brain mast cell enriched in the choroid plexus, and peripheral blood transferred to central nervous system (CNS). Histamine release by these cells may contribute to CSF histamine levels. Increased CSF histamine levels have been reported in meningitis and encephalitis (Ito 2010). In the demyelinating diseases, histamine levels of MS were low but those of ADEM were high. In addition, we found reductions in CSF histamine levels in PSP and CBD compared to MSA (Kanbayashi2012). The differences of histamine levels in these disorders may be caused by the dysfunctions of posterior hypothalamus. (2) Kleine-Levin Syndrome (KLS) is a neurological disorder characterized by recurring periods of excessive amounts of sleeping and eating. We hypothesized that this disorder is caused by the damage to hypothalamic neuropeptides. The refore, we measured hypothalamic peptides and neurotransmitters, such as, αMSH, AgRP, MCH, nesfatin-1, orexin and histamine. There were no specific findings in the levels of neuropeptides and neurotransmitters (Kanbayashi2010). While we found that CSF AgRP were elevated in the patients with anorexia nervosa, the histamine levels are relatively low among the patiets with KLS (Ito2010).

(1)我们首次报道了组胺在原发性CNS睡眠过度（如发作性睡病和特发性睡眠过度）中的作用降低（Kanbayashi 2009）。然而，其他疾病中的组胺水平仍然未知。我们还进一步测定了几种神经系统疾病脑脊液中组胺的含量。组胺能神经元只位于下丘脑后结节乳头核（TMN），并将其轴突投射到不同的脑区。组胺在脑内的释放不仅来自TMN组胺神经元，还来自脉络丛中富集的脑肥大细胞，以及外周血转移到中枢神经系统（CNS）。这些细胞释放的组胺可能有助于CSF组胺水平。据报告，脑膜炎和脑炎患者的CSF组胺水平升高（Ito 2010）。在脱髓鞘疾病中，MS的组胺水平较低，而ADEM的组胺水平较高。此外，我们发现与MSA相比，PSP和CBD的CSF组胺水平降低（Kanbayashi 2012）。这些疾病中组胺水平的差异可能是由下丘脑后部功能障碍引起的。(2)Kleine-Levin综合征（KLS）是一种神经系统疾病，其特征是反复出现过量的睡眠和进食。我们推测这种疾病是由下丘脑神经肽的损伤引起的。测定了下丘脑肽和神经递质α-MSH、AgRP、MCH、nesfatin-1、食欲素和组胺。神经肽和神经递质水平无特异性发现（Kanbayashi 2010）。虽然我们发现神经性厌食症患者的CSF AgRP升高，但KLS患者的组胺水平相对较低（Ito 2010）。

项目成果

Anti-NMDA-receptor antibody detected in encalitis, schizophrenia, and narcolepsy with psychotic features

在脑膜炎、精神分裂症和具有精神病特征的发作性睡病中检测到抗 NMDA 受体抗体

• 发表时间: 2012
• 期刊: BMC Psychiatry
• 影响因子: 4.4
• 作者: Ko Tsutsui;Takashi Kanbayashi;Keiko Tanaka;Shuken Boku;Wakako Ito;Jun Tokunaga;Akane Mori;Yasuo Hishikawa;Tetsuo Shiizu;Seiji Nishino
• 通讯作者: Seiji Nishino

EVALUATIONOF CSHISTAMININ THE PATIENTS WITH VARIOUS ATYPICAL PARKINSONIAN DISORDERS

各种非典型帕金森病患者的 CSHISTAMIN 评估

• 发表时间: 2012
• 期刊: SLEEP
• 影响因子: 5.6
• 作者: Kanbayashi T;Yasui K;Kodama T;Nomura T;Inomata Y;Yagisawa K;Yaegashi K;Kosaka M;Nakashima K;Shimizu T
• 通讯作者: Shimizu T

睡眠と体温調節

睡眠和温度调节

• 发表时间: 2010
• 期刊: 脳21
• 作者: 越前屋勝;清水徹男
• 通讯作者: 清水徹男

不眠

失眠

• 发表时间: 2008
• 期刊: エキスパートナース 24
• 作者: 尾崎章子;田ヶ谷浩邦
• 通讯作者: 田ヶ谷浩邦

診断確定までに約8年を要した抗NMDA受容体脳炎の1症例

一例抗NMDA受体脑炎，花了大约8年时间才确诊。

• 发表时间: 2011
• 期刊: 精神科
• 作者: 筒井幸;菊池結花;森朱音;湯浅稚子;三上学;神林崇;田中恵子;清水徹男
• 通讯作者: 清水徹男