Cultured human keratinocytes as a model for studying the dopamine metabolism in schizophrenia.

The dopamine hypothesis is the major etiological hypothesis of schizophrenia which proposes that enhanced central nervous system dopaminergic activity is the causative factor for this disease. The hypothesis remains unproven despite decades of research. The major difficulty in studying the disease is due to the unavailability of a suitable animal model. Studies with human blood, cerebrospinal fluid or post-mortem brains lead only to inconclusive results, due to the effects of medication and other environmental factors. No extra-neuronal cells, with the exception 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 dopamine. We have compared the properties of tyrosine hydroxylase, the rate-limiting enzyme, from mouse striatum and from human skin keratinocytes cultured in vitro. Moreover we could also detect dopamine beta hydroxylase and catechol-o-methyl transferase in keratinocytes. We propose that human keratinocytes cultured in vitro can be used to study the relevance of dopamine metabolism to schizophrenia under controlled conditions avoiding the effects of medication and other environmental factors.