Initial studies of embryonic transplants of human hippocampus and cerebral cortex derived from schizophrenic women.
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.
Department of Histology and Neurobiology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
R
R
Freedman
I
I
Strömberg
A
A
Seiger
L
L
Olson
A L
AL
Nordström
F A
FA
Wiesel
M
M
Bygdeman
C
C
Wetmore
M R
MR
Palmer
B J
BJ
Hoffer
D000328:Adult; D000818:Animals; D016380:Brain Tissue Transplantation / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor; D002540:Cerebral Cortex / Q000503:physiopathology / Q000637:transplantation*; D005260:Female; D016332:Fetal Tissue Transplantation / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology; D006085:Graft Survival / Q000235:genetics / Q000502:physiology; D006624:Hippocampus / Q000503:physiopathology / Q000637:transplantation*; D006801:Humans; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000502:physiology; D009693:Nucleic Acid Hybridization; D011247:Pregnancy; D051381:Rats; D011923:Rats, Nude; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology; D014183:Transplantation, Heterologous; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000235:genetics / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D005680:gamma-Aminobutyric Acid; D014446:Tyrosine 3-Monooxygenase