Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease

Table 1 Significant main effect of treatment (NBH, ME7, ME7 + JNJ527) across the cortex, thalamus and hippocampal regions

(A) [3H]PBR28 autoradiography
Mixed effects ANOVA factors
Treatment_{(NBH, ME7, ME7+JNJ527)}	F (2,20) = 40.14, p < 0.0001
ROI_{(cortex, hippocampus, thalamus)}	F (1.998, 39.96) = 11.90, p < 0.0001
Treatment × ROI	F (4,40) = 2.227, p = 0.0833
(B) TSPO immunohistochemistry
ROI	Main effect of treatment_{(NBH, ME7, ME7+JNJ527)}
Cortex	F (2,20) = 8.110, p = 0.0026
Thalamus	F (2,19) = 15.72, p < 0.0001
CA1 hippocampus	F (2,20) = 14.63, p = 0.0001
CA3 hippocampus	F (2,20) = 8.509, p = 0.0021
Dentate gyrus	F (2,20) = 16.30, p < 0.0001
(C) Immunofluoresence in the dentate gyrus
Marker	Main effect of treatment_{(NBH, ME7, ME7+JNJ527)}
TSPO	F (2,14) = 3.473, p = 0.0596
Iba 1	F (2,18) = 2.606, p = 0.0003
GFAP	F (2,20) = 1.096, p = 0.0017
NeuN	F (2,16) = 8.395, p < 0.0001
(D) Immunofluoresence co-localization in the dentate gyrus
Marker	Main effect of treatment_{(NBH, ME7, ME7+JNJ527)}
TSPO+ Iba1+	F (2,19) = 16.34, p < 0.0001
TSPO+ GFAP+	F (2,20) = 10.84, p = 0.0012
TSPO+ NeuN+	F (2,16) = 34.55, p < 0.0001
TSPO+ CD31+	F (2,15) = 2.099, p = 0.1571

(A) [3H]PBR28 autoradiography. Mixed-effects repeated measures analysis (F tests and corresponding p values) showing a significant main effect of treatment group (normal brain homogenate NBH, ME7 prion infected, and ME7 prion infected treated with JNJ527), a significant main effect of region of interest (ROI; cortex, hippocampus and thalamus) but no significant interaction between the two factors. (B) TSPO immunohistochemistry. F tests and corresponding p values for an unpaired one-way ANOVA in the cortex, thalamus and several regions in the hippocampus: CA1, CA3, dentate gyrus (DG). (C) TSPO, Iba1, GFAP and NeuN immunofluorescence. F tests and corresponding p values of the effects of treatment (NBH, ME7 and ME7 + JNJ527) for each marker in the DG. (D) Co-localization immunofluorescence analysis of TSPO with Iba1, GFAP, NeuN and CD31. F tests and corresponding p values of the main effect of treatment (NBH, ME7, ME7 + JNJ527) for each marker (TSPO and Iba1, TSPO and GFAP, TSPO and NeuN, TSPO and CD31)

ISSN: 1742-2094