Mechanisms of aluminium neurotoxicity in oxidative stress-induced ...

SUMMARY
SUMMARY
Aluminium has become an important health concern due to both the frequent
exposure to this metal and the suggested ability of aluminium to cause
neurodegeneration. Pathological conditions such as PD have been associated with the
accumulation of aluminium in brain. Although, aluminium is not a redox metal, it has
been reported to be able to enhance brain oxidative stress. However, the molecular
mechanism of its neurotoxicity remains not well understood. Consequently, we resolved
to gain insight into the mechanisms of aluminium neurotoxicity in oxidative stress-
induced degenerative processes in relation with PD.
Before starting the whole procedures with aluminium, it was crucial to establish
the kinetics of the oxidative damage induced in a 6-OHDA model of PD and also to
quantify the changes observed in the indices of lipid peroxidation and oxidant status of
proteins in striatum and ventral midbrain. These results would thereafter enable us to
decide at which exact post-injection time should be performed the measurement of
indices of brain oxidative stress when assessing the oxidative effects of aluminium. To
accomplish the first part of this thesis, we chose the unilateral and intrastriatal injection
of 6-OHDA to lesion the DAergic nigrostriatal pathway system in male Sprague-
Dawley rats. This procedure has been extensively used to examine the degeneration of
the DAergic neurons characteristics of PD. When compared to others 6-OHDA models
with injections into the SN or the nigrostriatal tract, this method mimics more closely
the progression of PD as it leads to a slower retrograde degeneration of the nigrostriatal
system over a period of several weeks (Sauer and Oertel 1994, Przedborski et al. 1995,
Lee et al. 1996, Shimohama et al. 2003). In fact, this allowed us to use different groups
of rats sacrificed at distinct post-injection times (from 5 min to 7 days). Our results
clearly indicated that unilateral and intrastriatal injection of 6-OHDA results in
increased levels of lipid peroxidation and protein oxidation in the ventral midbrain and
in the striatum. We observed for both areas an aument during the first 2 days post-
injection and values returned to near control levels at the 7 day post-injection. Peak
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