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Fig. 7 | Journal of Neuroinflammation

Fig. 7

From: A breakdown in microglial metabolic reprogramming causes internalization dysfunction of α-synuclein in a mouse model of Parkinson’s disease

Fig. 7

Microglia-specific TRPV1 deficiency attenuates microglial phagocytosis of α-synuclein in the SNpc of PFF-injected TRPV1flox/flox; Cx3cr1Cre mice. a Representative double-immunostaining images for p-α-syn (Ser129) (red) and microglia (green) in the SNpc. The white arrows point to p-α-syn-phagocytosing microglia. Three-dimensional reconstruction of microglia and p-α-syn (Ser129) was produced using Imaris software (n = 3, biological replicates). Scale bar, 25 μm or 5 μm, respectively. bg Quantification of volume of p-α-synuclein in microglia (b), volume of microglia (c), relative Iba-1 intensity (d), number of junctions (e), number of branches (f), average length of processes g in the SNpc of mice after intrastriatal PFF- or PBS-injection (n = 3–4 animals per group). Scale bars, 25 µm and 5 µm for low- and high-magnification images, respectively. h RNA-seq analysis of microglial gene expression in PBS- or PFF-injected TRPV1flox/flox mice and TRPV1flox/flox; Cx3cr1Cre mice. Heat map generated by hierarchical gene clustering based on genotypes (vertical, 278 microglial genes; horizontal, individual mouse samples; n = 3 mice per group). Cluster 1: proinflammatory genes. Cluster 2: homeostatic genes. i Differentially expressed genes associated with immune responses, antigen processing and presentation, and cell motility in the brain of TRPV1flox/flox or TRPV1flox/flox; Cx3cr1cre mice 6 months after intrastriatal injection with PFF (n = 3 mice per group). One-way ANOVA with Tukey’s multiple comparisons test bg) or Student’s t-test i were used for statistical analyses. Error bars represent mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001

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