Research Article

Functional Crosstalk between CB and TRPV1 Receptors Protects Nigrostriatal Dopaminergic Neurons in the MPTP Model of Parkinson’s Disease

Figure 4

Crosstalk between CB and TRPV1 inhibits glial activation and expression of proinflammatory cytokines in the SN of MPTP-treated mice in vivo. Mice were intraperitoneally given an injection of PBS or MPTP. All mice intraperitoneally received vehicle as controls or cannabinoid (CB) antagonist (AM251 or AM630; 0.1 mg/kg/day) for 1 day or 3 days at 30 min before capsaicin (C) and 1 hour before MPTP and a single injection of capsaicin (0.5 mg/kg) at 30 min before MPTP. (a) Real-time PCR analysis showing mRNA expression of proinflammatory mediators (IL-1β, TNF-α, and iNOS) in the SN. Mice were sacrificed, and the total RNA was isolated from SN one day after the last injection of MPTP or vehicle in the absence or presence of CAP and CB1/2 antagonists (AM251 or AM630) (refer to Figure 1(a)). Bars represent the of four samples. C: control; M: MPTP; MC: MPTP and capsaicin; MCA2: MPTP, capsaicin, and AM251; MCA6: MPTP, capsaicin, and AM630. , significantly different from control. &: significantly different from MPTP. # and ##, significantly different from MPTP and capsaicin (one-way ANOVA with the Neuman-Keuls post hoc test). (b, c) Photomicrographs of CD11b+ microglia and GFAP+ astrocytes in the SN of MPTP-treated mice in vivo. Mice that received PBS as a control (CON); capsaicin (C); MPTP (M); MPTP and capsaicin (MC); MPTP, capsaicin, and AM251 (MCA2); or MPTP, capsaicin, and AM630 (MCA6) were sacrificed 3 days after the last MPTP injection (refer to Figure 1(a)). Brains were removed and coronal sections (30 μm) were cut using a sliding microtome. Every sixth serial section was selected and immunostained with CD11b antibody for microglia (b) or GFAP antibody for astrocytes (c). Insets show higher magnifications of (b) and (c), respectively. These data are representative of five to six animals per group. Dotted lines indicate SNpc. Scale bars: (a) 300-500 μm; (b) 250-420 μm.