Freedman R, Strömberg I, Seiger A, Olson L, Nordström A L, Wiesel F A, Bygdeman M, Wetmore C, Palmer M R, Hoffer B J
Department of Histology and Neurobiology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Biol Psychiatry. 1992 Dec 15;32(12):1148-63. doi: 10.1016/0006-3223(92)90194-5.
Human fetal brain tissue was obtained from first-trimester elective abortions of two women who also had schizophrenia. Portions of the embryonic hippocampus or cerebral cortex were transplanted into the anterior eye chamber of immunologically compromised athymic nude rats. In this environment, embryonic brain tissue derived from normal women generally continues organotypic growth and development for many months. Although initial survival after transplantation was normal, the tissue derived from schizophrenic women manifested less robust growth. However, cells in the transplants showed typical neuronal differentiation, with development of different neuronal types, such as pyramidal cells, granule cells, and gamma-aminobutyric acid (GABA)-containing interneurons. Rhythmic electrical activity was also observed, indicative of some local synaptic organization. The presence of messenger RNA (mRNA) for brain-derived neuronotrophic factor (BDNF) was observed using in situ hybridization. The reason for the decreased rate of growth of these transplants remains unknown and the significance of the finding cannot be assessed from only two fetuses. However, these preliminary findings suggest that fetal transplants may be a useful model system for the detection of developmental pathogenic processes in the expression and transmission of schizophrenia.
人类胎儿脑组织取自两名患有精神分裂症的女性在孕早期进行的选择性堕胎手术。将部分胚胎海马体或大脑皮层移植到免疫功能低下的无胸腺裸鼠的前房。在这种环境下，来自正常女性的胚胎脑组织通常会持续数月进行器官型生长和发育。尽管移植后的初始存活情况正常，但来自精神分裂症女性的组织生长不如正常组织旺盛。然而，移植组织中的细胞显示出典型的神经元分化，出现了不同类型的神经元，如锥体细胞、颗粒细胞和含γ-氨基丁酸（GABA）的中间神经元。还观察到有节律的电活动，表明存在一些局部突触组织。通过原位杂交观察到了脑源性神经营养因子（BDNF）信使核糖核酸（mRNA）的存在。这些移植组织生长速度降低的原因尚不清楚，而且仅从两个胎儿的情况无法评估这一发现的意义。然而，这些初步发现表明，胎儿移植可能是用于检测精神分裂症表达和传播过程中发育致病机制的有用模型系统。
