Figure 8

Effect of intracerebral infusion of a Fzd receptor antagonist within the intact SNpc in the number of TH⁺ Nissl⁺ and Fluorojade-C (FJC) cell bodies. The effect of blocking Wnt/β-catenin signaling was assessed using the negative modulator of Wnt1 signaling, Dkk1 (1 μg/μl) or saline, unilaterally infused into the left intact SNpc, as described. Mice were sacrificed 1-7 days post-infusion, and the brains processed for TH⁺ Nissl⁺ cell counts (M) and Fluorojade C staining (FJC, N) in consecutive midbrain sections. A-L: Confocal images showing TH⁺ (green) neurons counterstained with DAPI (blu) of coronal midbrain sections at the level of the SNpc 1 day after unilateral saline (A-C) or 1 (D-F), 3 (G-I) and 7 (J-L) days after unilateral Dkk1 infusion. In Dkk1-infused mice, a decrease of TH⁺ immunofluorescent signal was observed starting 1 d (D) in the ipsilateral (E), but not contralateral (F), non-infused SN, with a peak TH⁺ loss at 3 days (see H compared to I), and a stabilization observed by 7 days (F). M. Total number of TH⁺ and Nissl⁺ counted throught the entire rostro-caudal axis of the SNpc. Treatment groups were averaged (n = 4/time-point, means ± S.E.M.) * p < 0.05 vs contralateral side, within each respective group. B. Total number of Fluorojade C (FJC) stained cells in SNpc ipsilateral and contralateral to the infusion was calculated for each side, averaged for each animal (n = 4/time-point) and normalized to the number of TH⁺ neurons in SNpc per section. *p < 0.05 vs saline injected side.