CULTURED SKIN FIBROBLASTS AS A CELL MODEL FOR INVESTIGATING SCHIZOPHRENIA

Cultured skin fibroblasts, among other non-neuronal cells (e.g. platel ets, lymphocytes, red blood cells), provide an advantageous system for investigating dynamic molecular regulatory processes underlying abnor mal cell growth, metabolism, and receptor-mediated signal transduction , without the confounding effects of disease state and its treatment i n a variety of brain disorders, including schizophrenia, and are usefu l for studies of systemic biochemical defects with predominant consequ ences for brain function. These cells are also useful for studying asp ects of neurotransmitter functions because the cells express enzymes i nvolved in their metabolism, as well as their receptors with complete machinery for signal transduction. These processes also function predi ctably with receptors that are transfected in fibroblasts. This review will focus on the use of cultured skin fibroblasts for studies of mol ecular mechanisms underlying the pathogenesis of schizophrenia, some o f which have also been studied in post-mortem brains. These mechanisms might involve DNA processing and mitogenesis, cell-cell adhesion mole cules, actions of growth factors, oxidative damage, and membrane phosp holipid derived second messengers. This review will further discuss th e implications of these processes to clinical and structural brain abn ormalities. An understanding of these biochemical processes might help establish therapeutic implications and identify the risk for illness through experimental strategies such as epidemiology, family pedigree and high risk populations. Finally, despite some methodological limita tions, skin fibroblasts are relatively easy to grow and maintain as pr imary cultures or as immortalized cell lines for long periods of time for use in investigating newly identified biochemical abnormalities. C opyright (C) 1996 Elsevier Science Ltd.