TRANSPLANT OF GABAERGIC NEURONS INTO THE SUBSTANTIA NIGRA OF KINDLED RATS

将伽巴能神经元移植到点燃大鼠的黑质中

• 批准号: 3901579
• 负责人: S NADI
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3901579
• 关键词: cerebellum; convulsions; embryo /fetus; epilepsy; gamma aminobutyrate; laboratory rat; microscopy; nervous system transplantation; neurons; stainings; substantia nigra

This project will investigate the effect of transplanting neuronal suspensions from the cerebellum of 16 day old rat embryos into the substantia nigra of adult kindled rats. The hypothesis is that the substantia nigra is involved in the control of spread of seizures and the addition of gamma amino butyric acid (GABA)ergic neurons to the nigra will prevent the seizures. GABAergic neurons are obtained by gentle trypsinization of the cerebellum of 16 days old embryos. These cells are then transplanted into the substantia nigra using a Harvard pump. The origin of the cells will be determined by staining with the glutamate decarboxylase (GAD) antibody as well as cerebellum specific antibodies. Our most recent results show at a light microscopic level a fine network of cells at the area of transplant in the nigra. These cells are elongated in shape with extensive processes. They have failed to stain with GAD antibody, but other GABAergic neurons in the area have not stained either. We are currently investigating the reasons behind this. Preliminary work has shown that kindling disappears for 2 weeks after transplant but then returns. The reasons for these findings are being investigated. The substantia nigra has been shown to be a controlling point of seizure spread by numerous investigators. The current study will attempt to demonstrate whether transplants of GABAergic neurons from rat embryo cerebellum will block the spread of seizures. The results of these studies were largely negative. The reasons for these findings could be multiple, among them the failure to be able to grow the GABAergic neurons and to form synapses. The conclusions of this study are that further basic knowledge of the neurobiology of brain transplants is needed before their usefulness in neurologic diseases can be evaluated.

该项目将研究神经移植的效果。 从16日龄大鼠胚胎的小脑悬液进入 成年点燃大鼠的黑质。我们的假设是 黑质参与控制癫痫发作的扩散和 黑质加入GABA能神经元 防止癫痫发作。 GABA能神经元是通过对小脑进行温和的胰酶消化而获得的 16天大的胚胎。然后将这些细胞移植到 用哈佛泵抽吸黑质。单元格的原点将是 谷氨酸脱羧酶(GAD)抗体染色测定 以及小脑特异性抗体。 我们最新的研究结果表明，在光镜水平上， 黑质移植区的细胞。这些细胞被拉长到 用广泛的工艺塑造。他们未能在GAD中染上污点 抗体阳性，但该区域其他GABA能神经元也未见染色。 我们目前正在调查这背后的原因。前期工作 已经表明点燃在移植后2周内消失，但随后 回归。这些发现的原因正在调查中。这个 黑质已被证明是癫痫蔓延的控制点。 被众多的调查人员。目前的研究将试图证明 大鼠胚胎小脑GABA能神经元移植是否会 阻止癫痫的蔓延。 这些研究的结果大多是负面的。出现这些情况的原因是 调查结果可能是多方面的，其中包括未能使 GABA能神经元和形成突触。这项研究的结论是 关于脑移植的神经生物学的更多基本知识是 在评估它们在神经系统疾病中的有效性之前，需要使用这些药物。