Injections were performed in the right mesencephalon dorsal to the nigra to minimize possible traumatic damage. Stereotaxic coordinates were − 5.4 mm anterior to bregma, − 1.9 mm right of midline, and − 7.0 mm ventral to the dura; tooth bar was at − 2.3 mm [23 ]. The viral vectors were injected using a 5-μl Hamilton syringe coupled to a motorized injector (Stoelting, Wood Dale, IL). Injections were accomplished in pulses of 0.5 μl/min (2 μl for the AAV9-WT α-syn-injected group and 1 μl for the AAV9-A53T α-syn-injected group), and once completed, the microsyringe was left in place for an additional time of 10 min before withdrawal, to avoid viral vector reflux through the injection tract. Groups of animals received oral treatment with the AT1 receptor antagonists candesartan (groups A2 and B2 1 mg/kg/day; AstraZeneca, Madrid, Spain) or telmisartan (groups B2 and B3; 1 mg/kg/day; Sigma, St. Louis, MO) from 2 weeks before AAV9 injection until they were sacrificed. The doses were selected on the basis of the results of our previous studies [24 (link), 25 (link)]. The powered drug was administered orally mixed with “Nocilla” hazelnut cream (Nutrexpa, Barcelona, Spain). Animals in control groups were given “Nocilla” hazelnut cream only.
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