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Fig. 10 | Cell & Bioscience

Fig. 10

From: Phosphodiesterase inhibition and Gucy2C activation enhance tyrosine hydroxylase Ser40 phosphorylation and improve 6-hydroxydopamine-induced motor deficits

Fig. 10

PDE inhibition and Gucy2C activation ameliorate impaired motor behavior in the 6-OHDA Parkinson’s disease mouse model. A Experimental Setup: Parkinson's disease model induction involved unilateral injection of 6-OHDA into the left striatum, causing unilateral degeneration of striatal dopaminergic terminals. On day 7, the first apomorphine rotations test assessed the efficacy of the lesions. Following the initial test, animals received three weeks of treatment with either vehicle, levodopa (L-DOPA), the PDE2A inhibitor (PF05180999), or the Gucy2C ligand (guanylin). Additional apomorphine-induced rotation tests were conducted after two and three weeks of treatment to evaluate the impact on motor behavior. Efficacy was measured by observing changes in rotation behavior, reflecting the effectiveness of the treatments. B Effect on motor behavior (rotations per 30 min) at day 7 following 6-OHDA induction (pre-treatment). All four 6-OHDA groups (n ≥ 11) exhibited significant increases in rotations compared to the sham group (n = 8), indicating the successful induction of motor deficits by 6-OHDA. C Effect on motor behavior (decrease in rotations compared to day 7 baseline) at day 21, following 2 weeks of treatment. Compared to 6-OHDA vehicle-treated animals (n = 12), L-DOPA (n = 12), PF05180999 (n = 11), and guanylin (n = 10) treatments demonstrate significant amelioration in motor complications. D Effect on motor behavior (decrease in rotations compared to day 7 baseline) at day 28, following 3 weeks of treatment. L-DOPA (n = 12), PF05180999 (n = 11), and guanylin (n = 6) treatments continue to show significant amelioration in motor complications compared to 6-OHDA vehicle-treated animals (n = 12)

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Cell & Bioscience

ISSN: 2045-3701

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