CULTURED HUMAN KERATINOCYTES AS A MODEL FOR STUDYING THE DOPAMINE METABOLISM IN SCHIZOPHRENIA

The dopamine hypothesis is the major etiotogical hypothesis of schizop hrenia which proposes that enhanced central nervous system dopaminergi c activity is the causative factor for this disease. The hypothesis re mains unproven despite decades of research. The major difficulty in st udying the disease is due to the unavailability of a suitable animal m odel. Studies with human blood, cerebrospinal fluid or post-mortem bra ins lead only to inconclusive results, due to the effects of medicatio n and other environmental factors. No extra-neuronal cells, with the e xception of adrenal medulla, have been reported to contain a dopamine metabolic pathway. Literature evidence and our own study suggest that human keratinocytes express the enzymes to synthesize and degrade dopa mine. We have compared the properties of tyrosine hydroxylase, the rat e-limiting enzyme, from mouse striatum and from human skin keratinocyt es cultured in vitro. Moreover we could also detect dopamine beta hydr oxylase and catechol-o-methyl transferase in keratinocytes. We propose that human keratinocytes cultured in vitro can be used to study the r elevance of dopamine metabolism to schizophrenia under controlled cond itions avoiding the effects of medication and other environmental fact ors.