ABNORMALITIES IN FIBROBLASTS OF SCHIZOPHRENIC PATIENTS

精神分裂症患者成纤维细胞异常

• 批准号: 3429356
• 负责人: SAHEBARAO P MAHADIK
• 金额: $ 5.52万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 1992-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3429356
• 关键词: behavior disorders; biopsy; bipolar depression; calcium; cell adhesion; cell bank /registry; cell cell interaction; cell growth regulation; cell transformation; epidermal growth factor; fibroblast growth factor; fibroblasts; fibronectins; human subject; morphology; pathologic process; schizophrenia; simian virus 40; tissue /cell culture

Fibroblast cell lines have been used to elucidate the pathophysiological mechanisms that may be relevant to central nervous system dysfunction in neuropsychiatric patients. In a preliminary study, we found growth parameters (initial growth and rate of growth) and morphology (size, shape and orientation) of the established fibroblasts of both schizophrenic and bipolar patients to markedly differ from normal subjects. Fibroblasts of patient grew at a much slower rate than fibroblasts of controls. We propose to conduct over a two year period, skin biopsies for obtaining fibroblast cell lines in 20 schizophrenic patients and 20 bipolar patients, both patient groups will be off neuroleptic treatment at the time of skin biopsies, and 20 normal controls matched for age, sex and ethnicity. The specific aims will be: 1. To establish primary cell-lines of skin fibroblasts, and immortalize them by cell transformation with SV-40 to establish a fibroblast cell depository, which will be expanded in future years, for their long-term use. 2. To establish growth parameters (initial growth, rate of growth and morphology) of fibroblast primary cultures and immortalized cultures from schizophrenic patients and compare them to growth parameters in fibroblast cultures from bipolar patients and normal controls. The altered growth patterns of cells in culture may be indicative of possible genetic/metabolic alterations. 3. To identify the possible molecular mechanisms associated with abnormal growth parameters: the adhesiveness to plastic substratum, the levels of fibronectin and the growth response to growth factors, e.g. epidermal growth factor and fibroblast growth factor will be studied. Thus, these cultures would potentially be useful for the study of relevant biochemical variability in CNS that may be associated with specific neuropathological and/or possibly behavioral changes in schizophrenic patients.

成纤维细胞系已被用于阐明病理生理 可能与中枢神经系统功能障碍相关的机制， 神经精神病患者 在初步研究中，我们发现 参数（初始生长和生长速率）和形态（大小、形状 和方向）的精神分裂症和 双相情感障碍患者与正常受试者明显不同。 成纤维细胞 患者的生长速度比对照组的成纤维细胞慢得多。 我们建议进行为期两年的皮肤活检， 20名精神分裂症患者和20名双相情感障碍患者的成纤维细胞系， 两组患者在皮肤脱落时均将停止精神抑制剂治疗 活组织检查，和20名年龄，性别和种族相匹配的正常对照。 的 具体目标是：建立皮肤原代细胞系 成纤维细胞，并通过用SV-40进行细胞转化使其永生化， 建立一个成纤维细胞库，今后将扩大该库 多年来，长期使用。 2.建立生长参数（初始 生长、生长速率和形态学），以及 精神分裂症患者的永生化培养物，并将其与 双相情感障碍患者和正常人成纤维细胞培养物的生长参数 对照 培养中细胞生长模式的改变可能是 表明可能的遗传/代谢改变。 3.识别 与异常生长参数相关的可能分子机制： 纤维连接蛋白水平和纤维连接蛋白水平， 对生长因子如表皮生长因子的生长反应， 将研究成纤维细胞生长因子。 因此，这些文化 潜在地可用于研究相关的生物化学变异性， 可能与特定神经病理学和/或可能 精神分裂症患者的行为变化