Effect of pharmacological activation of Wnt/β-catenin signaling in TH+ neuroprotection against intracerebral Dkk1 or systemic MPTP treatment. To mimick the activation of Wnt1/β-catenin signaling, we selected the specific GSK-3β inhibitor, AR (10 mg/kg twice a day) starting 72 h before unilateral Dkk1 infusion within the SN, or before the systemic (i.p.) treatment with the parkinsonian neurotoxin, MPTP (15 mg kg-1, 4 times a day at 2 h intervals), and mice sacrificed at the peak degeneration phase (3 days post-treatment). A-B: Representative confocal images showing dual localization of TH+ neurons (green) and GFAP+ astrocytes (red) in Saline (A), MPTP (B) and AR/MPTP (C) 4d post-MPTP, showing the sharp decrease of TH neurons associated to the marked astrocytosis and the remarkable protective effect of AR (C). C: The total number of TH+ and Nissl+ neurons was counted throught the entire rostro-caudal axis of the SNpc as above. Treatment groups were averaged (n = 4/time-point, means ± S.E.M.) * p < 0.05 vs unifused side (for Dkk1), within each respective group. Dkk1 and MPTP significantly reduced TH+ and Nissl+ neurons 4 d post-treatment. MPTP systemic treatment reduces TH+ neuron numbers in both left and both sides. Note the remarkable counteraction afforded by AR in increasing TH+ neurons to unlesioned saline-treated control. *p < 0.05 vs -MPTP.