Upregulation of NAD(P)H:Quinone Oxidoreductase (NQO1) in Glial Cells of 6-Hydroxydopamine-Lesioned Substantia Nigra in the Rat

Abstract

AbstractDopamine quinone toxicity has been implicated in the degeneration of nigral dopaminergic (DA) neurons in Parkinson’s disease (PD). NAD(P)H:quinone oxidoreductase (NQO1) may protect against this quinone toxicity. In Parkinsonian brains, levels of NQO1 are increased in reactive glia cells that are located around the remaining DA neurons in the substantia nigra pars compacta (SNc), suggesting a neuroprotective role of NQO1.It is not known at which stage of the disease process the upregulation of glial NQO1 starts. Furthermore, it is at present not clear whether NQO1 indeed plays a neuroprotective role in the disease process. As a first step to experimentally study a potential neuroprotective role of NQO1, it was examined whether activation of glia cells and changes in the distribution of NQO1-positive glia cells and the expression levels of glial NQO1, as seen in PD brains, also occurred in a 6-hydroxydopamine (6-OHDA) rat model of PD.Our results show that astroglia cells and microglia cells were activated. Furthermore, NQO1 was upregulated in astroglia cells in the SNc in those areas in which DA neurons degenerated. The time course and pattern of upregulation of NQO1 paralleled those of the degeneration of DA neurons. Activated microglia were seen at a later stage during the course of degeneration of DA neurons.In conclusion, in the present model, astroglia cells and microglia cells are activated in response to 6-OHDA-induced oxidative stress. Furthermore, levels of NQO1 are increased in astroglia cells. The findings in the present model are in line with the findings as seen in parkinsonian brains. The 6-OHDA rat model of PD is, therefore, suitable for further research to examine a potential neuroprotective role of NQO1.KeywordsTyrosine HydroxylaseAstroglia CellGlia CellGFAP ImmunoreactivityParkinsonian BrainThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.