Nigrostriatal lesion characterization and AIMs scores.
The rate-limiting enzyme in the dopamine synthesis pathway is TH, widely
accepted as a marker of dopaminergic neurons. We first examined
neurodegeneration in the striatum by TH-immunoreactivity in the brain
coronal sections of 6-OHDA-lesioned and control animals.
Rats with 6-OHDA lesion exhibited more than 90% reduction in
TH-immunostaining in the striatum and SNc compared to sham lesioned
animals (controls; Fig. 1A-D).
In the apomorphine-induced rotational behavior, rats presented strong
contralateral turns following apomorphine challenge (results not
presented) confirming >90% dopaminergic cell loss
In respect to chronic L-DOPA treatment, 90% of the rats developed AIMs
impacting the contralateral forelimb, orofacial movements and axial
dystonia (Fig. 1E, p<0.05, 6OHDA+Vehicle+L-DOPA). The maximum
total AIMs score was reached 60–120 min after L-DOPA administration and
gradually declined to the baseline level over 180 min (Fig. 1F).
Administration of a single dose of doxycycline (40mg kg-1), 30 min
before L-DOPA, significantly decreased AIMs (79%; Fig. 1E-F,6OHDA+Vehicle+L-DOPA AIMs score=122.41±24.5 vs.6OHDA+DOXY+L-DOPA ALO AIMs score=26.77±10.79, p<0.001)
over 20 to 140 min observation period (Fig. 1F). AIMs were not observed
in both the non-lesioned rats and lesioned rats treated with vehicle or
doxycycline (data not shown).