Differential expression of cytochrome P450 enzymes in cultured and intact foetal rat ventral mesencephalon.

Abstract

Genetic susceptibility to toxin action leading to nigral cell degeneration in Parkinson's disease (PD) may be dictated by the activity of P450 enzymes in brain. In adult rat brain only CYP2C13/6, CYP2D2, CYP2D5 are found in the substantia nigra. However, little is known concerning the isoforms present in foetal dopaminergic ventral mesencephalon (VM) tissues commonly used to study toxin action. In this investigation, we have determined the expression of P450 enzymes in foetal (VM) slices and in primary cultures of this region. In foetal VM sections immunoreactivity was observed for CYP2C13/6, CYP2D1, CYP2D3, CYP2D4, CYP2D5 and OR. There was no expression of CYP1A2, CYP2B1/2, CYP2C12, CYP2D2 and CYP2E1. In cultured foetal rat VM, immunoreactivity was observed for all P450 enzymes examined, namely CYP1A2, CYP2B1/2, CYP2C13/6, CYP2C12, CYP2D1, CYP2D2, CYP2D3, CYP2D4, CYP2D5, CYP2E1 and OR. There were marked differences in the degree of expression of the isoforms of P450, for example CYP2D1 was only weakly expressed in foetal VM sections but expression was strong in VM cultures. The difference between VM slices and primary cultures suggests that the culturing process can induce some P450 enzymes. CYP2D1, CYP2D3, CYP2D4 were expressed in the foetal VM but were not present in adult rat substantia nigra. Further investigation is now required to determine the functional implications as they may confer an altered level of susceptibility to neurotoxins between foetal and adult dopaminergic cells.