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喹啉酸损伤大鼠新纹状体中胎儿纹状体移植体中免疫反应性γ-氨基丁酸、脑啡肽和还原型辅酶Ⅱ-黄递酶阳性神经元的定位

Localization of immunoreactive GABA and enkephalin and NADPH-diaphorase-positive neurons in fetal striatal grafts in the quinolinic-acid-lesioned rat neostriatum.

作者信息

Roberts R C, Difiglia M

机构信息

Department of Neurology, Massachusetts General Hospital, Boston 02114.

出版信息

J Comp Neurol. 1988 Aug 15;274(3):406-21. doi: 10.1002/cne.902740309.

Abstract

Fetal striatal tissue grafts have been shown to partially reverse the biochemical and behavioral deficits induced by excitotoxic lesions. To determine if grafted striatal neurons contain neurochemical markers similar to those in neurons in the caudate nucleus and to establish the morphological characteristics and relative frequency of labeled neurons in the grafts, the localization of immunoreactive GABA and leucine-enkephalin (ENK) and of NADPH-diaphorase (NADPH-d) activity was examined in fetal striatal grafts at the light and electron microscopic levels. Striatal tissue from 17-day fetuses was grafted into the caudate nucleus of adult rats 1 week after intracaudate injections of either a low or high dose of quinolinic acid. At the light microscopic level, immunoreactive GABA and ENK and NADPH-d-positive neurons, processes, and punctate structures were present within adjacent sections of the same grafts. The frequency and morphological features of these labeled cell populations were similar in grafts placed into either minimally or extensively lesioned striata. Immunoreactive GABA and ENK neurons in the grafts constituted 28% and 13.5%, respectively, of the neuronal population of the graft and their mean diameters were 22 and 14% larger, respectively, than neostriatal neurons that contained the same chemical markers. NADPH-d-positive neurons in the grafts formed 3.5% of total grafted neurons and exhibited characteristics of neostriatal NADPH-d-containing aspiny cells, including medium-sized somata, indented nuclei, and varicose dendrites. At the electron microscopic level most GABA-positive neurons in the grafts contained indented nuclei and most immunoreactive ENK somata had unindented nuclei. Dendrites and dendritic spines with GABA or ENK immunoreactivity were present in the grafts where they were postsynaptic to unlabeled axons. Immunoreactive GABA and ENK axon terminals formed synapses with unlabeled neuronal profiles in the grafts. These findings demonstrate that fetal striatal grafts contain chemically defined neuronal populations that form synaptic connections within the graft and share some features with corresponding cell groups in the neostriatum. These results provide an anatomical basis for the graft-induced recovery from behavioral and biochemical deficits caused by instrastriatal lesions reported in other studies.

摘要

胎儿纹状体组织移植已被证明能部分逆转由兴奋性毒性损伤引起的生化和行为缺陷。为了确定移植的纹状体神经元是否含有与尾状核神经元相似的神经化学标记物,并确定移植中标记神经元的形态特征和相对频率,我们在光镜和电镜水平上检测了胎儿纹状体移植中免疫反应性γ-氨基丁酸(GABA)、亮氨酸脑啡肽(ENK)以及还原型辅酶Ⅱ黄递酶(NADPH-d)活性的定位。在尾状核内注射低剂量或高剂量喹啉酸1周后,将17天胎儿的纹状体组织移植到成年大鼠的尾状核中。在光镜水平上,同一移植块的相邻切片中存在免疫反应性GABA、ENK以及NADPH-d阳性神经元、突起和点状结构。在植入轻度或广泛损伤纹状体的移植块中,这些标记细胞群体的频率和形态特征相似。移植中的免疫反应性GABA和ENK神经元分别占移植神经元群体的28%和13.5%,它们的平均直径分别比含有相同化学标记物的新纹状体神经元大22%和14%。移植中的NADPH-d阳性神经元占移植神经元总数的3.5%,表现出新纹状体含NADPH-d的无棘细胞的特征,包括中等大小的胞体、凹陷的细胞核和曲张的树突。在电镜水平上,移植中的大多数GABA阳性神经元含有凹陷的细胞核,大多数免疫反应性ENK胞体具有未凹陷的细胞核。移植中存在具有GABA或ENK免疫反应性的树突和树突棘,它们是未标记轴突的突触后结构。免疫反应性GABA和ENK轴突终末与移植中未标记的神经元轮廓形成突触。这些发现表明,胎儿纹状体移植含有化学定义的神经元群体,这些群体在移植内形成突触连接,并与新纹状体中的相应细胞群具有一些共同特征。这些结果为其他研究中报道的移植诱导从纹状体内损伤引起的行为和生化缺陷中恢复提供了解剖学基础。

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