Parkinson's disease (PD) involves the loss of striatal dopaminergic neurons, although other
neurotransmitters and brain areas are also involved in its pathophysiology. In rodent models to PD it has been shown
statins improve cognitive and motor deficits and attenuate inflammatory responses evoked by PD-related toxins.
Statins are the drugs most prescribed to
hypercholesterolemia, but
neuroprotective effects have also been attributed to
statins treatment in humans and in animal models. This study aimed to establish an in vitro model of
6-hydroxydopamine (6-OHDA)-induced toxicity, used as an initial screening test to identify effective drugs against neural degeneration related to PD. The putative
neuroprotective effect of
atorvastatin against 6-OHDA-induced toxicity in rat striatal, cerebrocortical and hippocampal slices was also evaluated.
6-OHDA (100μM) decreased cellular viability in slices obtained from rat cerebral cortex, hippocampus and striatum.
6-OHDA also induced an increased
reactive oxygen species (ROS) production and
mitochondrial dysfunction. Co-incubation of
6-OHDA with
atorvastatin (10μM) or
MK-801 (50μM) an
N-methyl-d-aspartate (
NMDA) receptor antagonist, partially attenuated the cellular damage evoked by
6-OHDA in the three brain areas.
Atorvastatin partially reduced ROS production in the hippocampus and striatum and disturbances of mitochondria membrane potential in cortex and striatum. 6-OHDA-induced toxicity in vitro displays differences among the brain structures, but it is also observed in cerebrocortical and hippocampal slices, besides striatum.