Parkinson‘s disease (PD) is a common neurodegenerative disease that
affects mainly elderly people. It is characterized by the progressive cell death of
dopaminergic neurons in the nigrostriatal system, which causes the development
of the classic tetrad of symptoms: resting tremor, muscular rigidity, bradikynesia
and postural instability. There is evidence that both genetic and environmental
factors play a role in the development of the disease. In order to better understand
the mechanisms undelying this disease, several animal models have been used to
mimic some aspect of the dopaminergic degeneration. The intracerebral injection
of 6-OHDA has been one of the most used PD model. This toxin is preferentially
injected into the striatum or in the substantia nigra to provoke a selective
degeneration of dopaminergic neurons from the nigrostriatal pathway. When a
unilateral injection is used, the animals display a stereotypical rotational behavior
after pharmacological induction, and such behavior has been largely used as a
measure of the degree of nigroestriatal degeneration. This model is well
characterized in rats and has been an useful tool to test neuroprotective therapies.
Mice, as much as rats, are also largely used in studies of DP, but the 6-OHDA
model has not been well described. The objective of the present work was to
improve the characterization of the hemiparkinsonism model based on a single
unilateral intraestriatal injection of 6-OHDA in C57BL6 mice, to provide a more
detailed evaluation of the temporal course of the neuronal dopaminergic
degeneration in the substantia nigra and to establish the degree of correlation
between the degeneration and behavioral changes. Our results showed that a
single injection of 10 μg of 6-OHDA into the striatum causes progressive
degeneration of nigral dopaminergic neurons dependent of survival time, and that
there is a high correlation between the rate of degeneration and the rotational
behavior induced by apomorphine. Spontaneous motor behaviors such as
ambulation and rearing had a lower correlation with the degeneration. Therefore,
we suggest that the rotational behavior induced by apomorphine provides a good
measure of the degree of asymmetry in the nigrostriatal pathway of mice with 6-
OHDA-induced hemiparkinsonism and that it can indeed be an useful tool in
experiments to test therapies with neuroprotective potential for Parkinson’s
disease.
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