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，特别是多巴胺能 来自黑质和谷氨酸能神经元的传入 来自大脑皮层的传入神经。采用的技术包括： (I)含儿茶酚胺或L-多巴的细胞移植(即， 转基因细胞和从胚胎脑组织中获得的细胞) 进入大脑，(Ii)生化和药理学研究，以及(Iii) 使用组织培养模型的研究。这些实验的目的是 部分是为了：(A)阐明这些细胞在 移植与宿主脑对移植脑的反应 以及(B)研究神经元适应的机制和 对损伤和慢性药物治疗反应的可塑性。 具体地说，这些实验使用动物模型来：(1)开发 脑组织移植技术的临床应用 帕金森氏症；(2)开发脑组织移植技术 这最终可能适用于其他疾病，如 精神分裂症和癫痫，如果这些障碍变成 充分了解以允许此类应用；(3)开发 替代细胞类型，如永生化神经元，用于移植 进入大脑及相应的体外细胞模型研究 分化和细胞间的相互作用；以及(4)阐明这些因素 控制大脑发育和大脑对损伤或损伤的反应， 特别强调黑质纹状体的多巴胺系统。在.期间 在上一个报告年度，在这些方面取得了重大进展 区域。

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 cells containing catecholamines or L-DOPA (i.e., genetically altered cells and cells obtained from 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 cells 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, 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. During the past reporting year, significant progress has been made in these areas.