BRAIN TISSUE TRANSPLANTATION

这个项目涉及到可塑性和功能后果的研究。 纹状体传入系统的变化，特别是 来自黑质和黑质的多巴胺能传入 谷氨酸能传入神经来源于大脑皮层。技术 使用涉及：(1)移植含儿茶酚胺的组织 或者L-多巴(即肾上腺髓质，肿瘤细胞，转基因 细胞和胚胎脑组织)进入大脑，(Ii)生化和 药理研究，以及(Iii)使用组织培养模型的研究。 这些实验的部分目的是：(A)阐明 移植后这些组织的特性及移植后的反应 将宿主脑转移到移植组织，以及(B)调查 损伤反应中的神经元适应和可塑性机制 和慢性药物治疗。具体地说，(一)这些 实验使用动物模型来：(1)发展技术 脑组织移植在帕金森氏病的临床应用； (2)开发脑组织移植技术，最终 可能适用于其他障碍，如精神分裂症和 癫痫，如果以及当这些疾病得到充分了解的时候 以允许这种应用；(3)开发替代细胞类型，例如 永生化神经元，用于移植到大脑中 相应的细胞分化和细胞分化体外模型研究 细胞间的相互作用；以及(4)阐明控制大脑的因素 发育和大脑对损伤或损伤的反应，特别是 强调黑质纹状体的多巴胺系统。(B)第二个目的 这些实验的主要目的是阐明相互作用 谷氨酸介导的皮质纹状体系统的功能 和相关的解剖系统，以及(B)多巴胺能系统，包括 黑质纹状体系统；刺激剂和 抗精神病药物。这些研究的最终目的是加强 我们对抗精神病药作用模式的理解 精神分裂症患者的脑功能障碍。次要目的是增强 我们对刺激性药物作用机制的理解和 酒精成瘾；开发具有潜在治疗作用的化合物 兴奋剂过量、精神分裂症和癫痫的急性治疗 疾病；并了解可能的形式的可塑性在 皮质纹状体系统。在过去一年的报告中， 在这些领域已经取得了进展。

This project involves studies of plasticity and functional consequences of changes in the striatal afferent systems, especially the dopaminergic afferents derived from the substantia nigra and the glutamatergic afferents derived from the cerebral cortex. Techniques employed involve: (i) transplanting tissues containing catecholamines or L-DOPA (i.e., adrenal medulla, tumor cells, genetically altered cells, and embryonic brain tissue) into the brain, (ii) biochemical and pharmacological studies, and (iii) studies using tissue culture models. The purpose of these experiments is in part to: (A) elucidate the properties of these tissues after transplantation and the response of the host brain to the transplanted tissues, and (B) to investigate mechanisms of neuronal adaptation and plasticity in response to injury and chronic pharmacological treatments. Specifically, (A) these experiments employ animal models to: (1) develop the techniques of brain tissue transplantation for clinical use in Parkinson's disease; (2) develop brain tissue transplantation techniques which eventually may be applicable to other disorders such as schizophrenia and epilepsy, if and when these disorders become sufficiently understood to permit such applications; (3) develop alternate cell types, such as immortalized neurons, for transplantation into the brain and corresponding in vitro model studies of cellular differentiation and cell-cell interactions; and (4) elucidate the factors controlling brain development and brain response to injury or impairment, with particular emphasis on the nigrostriatal dopamine system. (B) The second purpose of these experiments is primarily aimed at elucidating the interactions between functions of: (a) the glutamate-mediated corticostriatal system and related anatomical systems, and (b) dopaminergic systems, including the nigrostriatal system; and the functional effects of stimulant and neuroleptic drugs. The ultimate purpose of these studies is to enhance our understanding of the mode of action of neuroleptics and possibly brain dysfunction in schizophrenia. Secondary purposes are to enhance our understanding of the mechanisms of stimulant drug effects and alcohol addiction; to develop compounds with potential utility for the acute treatment of stimulant overdose, schizophrenia, and seizure disorders; and to understand the possible forms of plasticity in the corticostriatal system. During the past reporting year, significant progress has been made in these areas.