A Study on Brainstem Monoaminergic Neuron System in Developmental Disorders

发育障碍中脑干单胺能神经元系统的研究

• 批准号: 09670860
• 负责人: ITOH Masahiro
• 金额: $ 0.64万
• 依托单位: Tokyo Metropolitan Institute for Neuroscience
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670860/
• 关键词: Development; Brainstem; Catecholamines; All-night polysomnography; Leigh disease; Severely handicapped; Infantile spasm; Lissencephaly; セロトニン; 聴覚伝達路; エンケファリン; Leigh脳症; 基底核

1). We compared sleep parameters in all-night polysomnography (PSG) with pathological findings of the brainstem in a two-year-old male child, showing the similar neuropathological distribution to that in Leigh disease. In PSG, the percentage of slow wave sleep was reduced, while that of REM sleep was within normal range. The average frequency of submental muscle twitches showed a mild decrease, although the number of rapid eye movements was preserved. The tone of submental muscle was maintained and suppressed during non-REM and REM sleep, respectively. The sleep parameters were less affected than in Leigh disease. Neuropathologically, both the number of neurons and the percentage of tyrosine hydroxylase (TH)-immunopositive neurons were reduced in the locus ceruleus of the patient, however, the brainstem lesions were not so severe as those in Leigh disease. These data suggested that there might be a correlation between physiological dysfunctions and pathological changes in the human brainstem.2). To investigate the involvement of the brainstem lesion in the pathological mechanism of infantile spasm, we immunohistologically examined the expressions of neurotransmitters and calcium-binding proteins in the brainstem in autopsy cases who suffered from both West and Lennox-Gastaut syndromes (WL), consisting of four subjects each of lissencephaly and a sequela of perinatal hypoxic ischemic encephalopathy. TH-immunopositive neurons were reduced in the dorsal motor nucleus of the vagal nerve in all of the WL patients, while most of tryptophan hydroxylase-immunopositive structures were preserved. In the anti-parvalbumin (PV) immunostaining, the brainstem auditory system was poorly identified in the WL patients. It is more likely that the disturbance of immunoreactivities for TH and PV observed in our WL autopsy cases can be related to the pathogenesis of infantile spasm, because the disease controls did not show any changes in either of immunostainings against TH and PV.

1)。我们比较了一名两岁男童的整夜多导睡眠图(PSG)中的睡眠参数与脑干的病理结果，显示出与Leigh病相似的神经病理分布。PSG组慢波睡眠百分比减少，REM睡眠百分比在正常范围内。虽然眼球快速运动的数量得到了保留，但颧下肌肉抽动的平均频率显示出轻微的下降。在非快速眼动睡眠和快速眼动睡眠中，分别维持和抑制了智下肌的张力。睡眠参数受到的影响小于Leigh病。神经病理学上，患者蓝斑内神经元数量和酪氨酸羟化酶(TH)免疫阳性神经元百分比均减少，但脑干病变不像Leigh病那样严重。这些数据表明，人类大脑的生理功能障碍和病理变化之间可能存在关联。为了探讨脑干病变在婴儿痉挛发病机制中的作用，我们用免疫组织化学方法检测了West综合征和Lennox-Gastaut综合征(WL)尸检病例脑干中神经递质和钙结合蛋白的表达，其中包括4例无脑和1例围产期缺氧缺血性脑病后遗症。所有WL患者迷走神经背侧运动核内TH免疫阳性神经元减少，而色氨酸羟化酶免疫阳性结构大部分保留。在抗小白蛋白(PV)免疫染色中，WL患者的脑干听觉系统的辨别能力较差。在我们的WL尸检病例中观察到的TH和PV免疫反应紊乱更有可能与婴儿痉挛的发病机制有关，因为疾病对照中针对TH和PV的免疫染色没有显示任何变化。

项目成果

Araki S, Hayashi M, Yasaka A.: "Electrophysiological brainstem dysfunction in a child with Leigh disease" Pediatric Neurology. Vol.16. 329-333 (1997)

Araki S、Hayashi M、Yasaka A.：“Leigh 病儿童的脑干电生理功能障碍”小儿神经病学。

Hayashi M,Kurota K,Suzuki K et al.: "Mcgelcncepholy, hydrocepholcs and cortfcol dysplosio in sauere dwatism mimcking lepreduvirism" Acta Neuro pothologico. 95・4. 431-436 (1998)

Hayashi M、Kurota K、Suzuki K 等人：“模拟麻风病的脑胶质瘤、脑积水和皮质发育不良”Acta Neuro potologico 95・436。

林 雅晴,伊東昌弘,森松義雄他: "重症心身障害児剖検脳における二次的神経変性" 日本重症心身障害学会誌. 22・1. 61-63 (1997)

Masaharu Hayashi、Masahiro Ito、Yoshio Morimatsu 等：“患有严重精神和身体残疾的儿童尸检大脑中的继发性神经变性”日本严重心身疾病学会杂志 22・1（1997 年）。