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

Experimental models of PD
INTRODUCTION
Animal models are invaluable tools to understand the pathophysiology and
motor deficits occurring in PD disease. Furthermore, they are also fundamental to create
new neuroprotective strategies and therapeutic interventions to improve symptomatic
management. Since PD does not develop spontaneously in animals, various models
have been developed in distinct species in order to mimic the characteristic functional
changes observed in PD. These include toxin-based models, gene-based models and
inflammation-based models.
Toxin-induced models
6-OHDA, the first animal toxin-based model of PD associated with loss of
DAergic neurons in the SNpc was introduced more than 40 years ago (Ungerstedt
1968). Since then many different neurotoxins, such as MPTP, paraquat and rotenone
have been used to induce DAergic neurodegeneration in animal models.
6-OHDA
The discovery of 6-OHDA toxicity toward catecholaminergic neurons initiated
the epoch of toxin-based models of PD (Ungerstedt 1968, Ungerstedt and Arbuthnott
1970). As 6-OHDA does not cross the BBB it must be administered directly in the brain
by local stereotaxic injection into the SN, median forebrain bundle (MFB), or striatum,
with the contralateral side serving as control, or by peripheral administration in neonatal
rats (Perese et al. 1989, Przedborski et al. 1995, Rodriguez-Pallares et al. 2007,
Sánchez-Iglesias et al. 2007a). 6-OHDA injection into the striatum leads to a more
progressive and slower degeneration of nigrostriatal neurons, which lasts for 1-3 weeks
(Sauer and Oertel 1994, Przedborski et al. 1995, Fleming et al. 2005), while injections
into SN or the nigrostriatal tract result in striatal DA depletion 2 to 3 days later (Faull
and Laverty 1969). The quantity of neurotoxin used, the site of injection, and the
different sensitivity between animal species determines the extent of the lesion.
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