TRANSPLANTATION OF CHOLINERGIC NERVE CELLS

胆碱能神经细胞移植

• 批准号: 3409124
• 负责人: WALTER C LOW
• 金额: $ 12.24万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3409124
• 关键词: acetylcholinesterase; basal ganglia; central nervous system; choline acetyltransferase; ciliary ganglion; electrophysiology; electrostimulus; embryo /fetus transplantation; evoked potentials; hippocampus; histochemistry /cytochemistry; innervation; learning; nervous system transplantation; neural degeneration; neuropsychology; parasympathetic nervous system; statistics /biometry; ventral column

Recent studies of fetal transplants containing cholinergic nerve cells of the rat septal nucleus have shown that the transplants have the capacity to innervate the hippocampal formation of recipient rats. The pattern of reinnervation appears to be quite specific and mimics the pattern produced by intrinsic septal afferents. Electrophysiological studies suggest that the transplant-derived innervation forms functional connections. This notion is further supported by behavioral studies that have demonstrated a recovery of maze learning abilities by rats with septal tissue transplanted into the denervated hippocampal formation. These studies in conjunction with other transplantation studies have led to the proposed use of neural transplants in the treatment of neurological disorders that stem from the degeneration specific neuronal populations. We propose to determine whether alternate sources of cholinergic nerve cells from the peripheral and central nervous system can innervate the hippocampal formation and form functional connections. Ciliary ganglia, ventral spinal cord, and basal nuclei from fetal rats; and ciliary ganglia and basal nuclei from adult rats will be grafted or implanted as cell suspensions into the hippocampal formation of adult rats. Evidence for the cholinergic innervation of the hippocampus will be obtained from histochemical methods to reveal acetycholinesterase and choline acetyltransferase localization and from assays to determine choline acetyltransferase activity. The functional nature of the transplant-derived innervation will be assessed by electrically stimulating the transplant and recording the evoked responses within the hippocampal formation, and by analyzing the slow- wave activity in behaving animals. Recovery of behavioral function will be determined by assessing the T-maze and water maze learning abilities of rats with and without transplants. These studies will determine whether alternate sources of cholinergic nerve cells can innervate target sites in the host hippocampal formation and restore functions normally mediated by cholinergic septal fibers.

含胆碱能神经胎儿移植的研究进展 大鼠隔核的细胞表明， 有能力支配海马结构， 受体大鼠 神经再支配的模式 特异性，并模仿固有间隔产生的模式， 传入神经 电生理学研究表明， 移植源性神经支配形成功能性连接。 这 这一观点得到了行为研究的进一步支持， 证明了大鼠迷宫学习能力的恢复， 隔组织移植到失神经支配的海马 阵 这些研究与其他 移植研究已经导致了神经移植的建议使用。 移植在治疗神经系统疾病， 从变性特异性神经元群体中分离出来。 我们建议确定是否有其他来源的胆碱能 来自外周和中枢神经系统的神经细胞可以 神经支配海马结构， 连接. 睫状神经节、腹侧脊髓和基底核 睫状神经节和基底核来自成年大鼠 将大鼠作为细胞悬浮液移植或植入到 成年大鼠海马结构。 胆碱能的证据 海马的神经支配将从 乙酰胆碱酯酶和胆碱组织化学方法 乙酰转移酶定位和测定 胆碱乙酰转移酶活性。 的职能性质 移植源性神经支配将通过电刺激来评估。 刺激移植物并记录诱发反应 在海马结构中，通过分析慢- 行为动物的波动活动。 行为恢复 功能将通过评估T-迷宫和水 有和没有移植的大鼠的迷宫学习能力。 这些研究将确定是否有其他来源的 胆碱能神经细胞可以支配宿主中的靶位点 海马形成和恢复正常介导的功能 由胆碱能隔纤维引起