Journal: Journal of Neuroinflammation

Article Title: Retention of normal glia function by an isoform-selective protein kinase inhibitor drug candidate that modulates cytokine production and cognitive outcomes

doi: 10.1186/s12974-017-0845-2

Figure Lengend Snippet: Selective attenuation of proinflammatory cytokines by MW150 administration in APP/PS1 KI mice cortex. a 11–12-month-old wild type ( WT ) or APP/PS1 knock-in ( KI ) mice were treated with saline vehicle ( veh ) or 2.5 mg/kg MW150 by intraperitoneal injection (i.p.) once daily for 14 days. b IL-1β was increased in KI + veh mice compared to WT + veh mice ( p = 0.0012), and MW150 treatment of KI mice (KI + MW150) significantly attenuated IL-1β levels compared to KI + veh ( p = 0.0243) ( F (2,38) = 6.46; p = 0.004). c TNFα was elevated in KI + veh mice compared to WT + veh and attenuated in KI + MW150 mice compared to KI + veh; however, these changes were not significant ( F (2,38) = 1.11; p = 0.34). d IL-6 was slightly elevated in KI + veh compared to WT + veh mice, and there was no effect of MW150 treatment ( n = 11 WT + veh; n = 14 KI + veh; n = 14 KI + MW150). Data are mean ± SEM. Source data is available in Additional file : Table S1

Article Snippet: Fig. 6 Effect of MW150 treatment on microglia closely associated with Aβ plaques and microglia-internalized Aβ in the cortex of APP/PS1 KI mice. a Representative images of Imaris 3D reconstruction of plaques.

Techniques: Knock-In, Saline, Injection

Journal: Journal of Neuroinflammation

Article Title: Retention of normal glia function by an isoform-selective protein kinase inhibitor drug candidate that modulates cytokine production and cognitive outcomes

doi: 10.1186/s12974-017-0845-2

Figure Lengend Snippet: No effect of MW150 on GFAP immunostaining. a Representative images of GFAP immunohistochemical (IHC) staining in cortex of WT or APP/PS1 KI mice treated with vehicle ( veh ) or MW150. b Digital quantification of GFAP in the cortex was done using the Aperio ScanScope with the entire cortex used as the region of interest. Quantification using the positive pixel algorithm showed a significant increase in GFAP staining in the KI + veh compared to WT + veh ( p < 0.0001). No significant difference was found between the KI + veh compared to the KI + MW150. (F2,41) = 34.66; p < 0.0001). ( n = 14 WT + veh; n = 14 KI + veh; n = 14 KI + MW150). Data are mean ± SEM. Source data is available in Additional file : Table S2

Article Snippet: Fig. 6 Effect of MW150 treatment on microglia closely associated with Aβ plaques and microglia-internalized Aβ in the cortex of APP/PS1 KI mice. a Representative images of Imaris 3D reconstruction of plaques.

Techniques: Immunostaining, Immunohistochemical staining, Immunohistochemistry, Staining

Journal: Journal of Neuroinflammation

Article Title: Retention of normal glia function by an isoform-selective protein kinase inhibitor drug candidate that modulates cytokine production and cognitive outcomes

doi: 10.1186/s12974-017-0845-2

Figure Lengend Snippet: No effect of MW150 on IBA1 + microglia volume. a Representative 3D surface reconstructions of IBA1 + cells generated from confocal microscopic imaging using Imaris software. b Mean volume ± standard deviation (SD) of rendered IBA1 cells is shown for the APP/PS1 KI + veh and APP/PS1 KI + MW150 groups. Data represent mean of 3–4 independent z-stacks from each mouse. ( n = 11 KI + veh; n = 14 KI + MW150)

Article Snippet: Fig. 6 Effect of MW150 treatment on microglia closely associated with Aβ plaques and microglia-internalized Aβ in the cortex of APP/PS1 KI mice. a Representative images of Imaris 3D reconstruction of plaques.

Techniques: Generated, Imaging, Software, Standard Deviation

Journal: Journal of Neuroinflammation

Article Title: Retention of normal glia function by an isoform-selective protein kinase inhibitor drug candidate that modulates cytokine production and cognitive outcomes

doi: 10.1186/s12974-017-0845-2

Figure Lengend Snippet: No effect of MW150 on CD45 and CD68 immunostaining in the cortex. a Representative images of CD45 IHC in cortex of wild type ( WT ) or APP/PS1 KI mice treated with saline vehicle ( veh ) or MW150. Digital quantification of CD45 in the cortex was done using the Aperio ScanScope, and the positive pixel algorithm. b CD45 was significantly increased in the KI + veh compared to the WT + veh treated mice ( p < 0.0001), with no effect of MW150 treatment. ( F (2,42) = 211.08; p < 0.0001). c Representative images of CD68 IHC. d CD68 was significantly increased in the KI + veh compared to the WT + veh-treated mice ( p < 0.0001), with no effect of MW150 treatment. ( F (2,42) = 28.81; p < 0.0001). ( n = 14 WT + veh; n = 14 KI + veh; n = 14 KI + MW150). Data are mean ± SEM. Source data is available in Additional file : Table S2

Article Snippet: Fig. 6 Effect of MW150 treatment on microglia closely associated with Aβ plaques and microglia-internalized Aβ in the cortex of APP/PS1 KI mice. a Representative images of Imaris 3D reconstruction of plaques.

Techniques: Immunostaining, Saline

Journal: Journal of Neuroinflammation

Article Title: Retention of normal glia function by an isoform-selective protein kinase inhibitor drug candidate that modulates cytokine production and cognitive outcomes

doi: 10.1186/s12974-017-0845-2

Figure Lengend Snippet: Effect of MW150 treatment on microglia closely associated with Aβ plaques and microglia-internalized Aβ in the cortex of APP/PS1 KI mice. a Representative images of Imaris 3D reconstruction of plaques. A region of interest ( ROI ) was generated by expanding the plaque volume by a 15 μm radius from the edge of the large plaques (larger than 10,000 voxels). This 3D ROI (shown in gray ) included the Aβ plaque, and a region near the plaque. IBA1 + cells in this ROI (shown in cyan ) were surface rendered to create a 3D volume of all IBA1 positive staining in the ROI. The IBA1 positive staining in the 3D ROI distinguishes plaque-associated microglia (shown in cyan ) compared to microglia away from plaques (shown in green ). b Volume of surface rendered IBA1 + cells within 15 μm radius around large plaques was significantly increased in KI + MW150 mice compared to KI + veh treatment ( p = 0.0397). c Representative image of microglia reconstruction with DAPI stained nuclei showing 6E10 staining within IBA1 + cell cytoplasm. d Microglia-internalized Aβ, as measured by 6E10 staining within surface rendered IBA1 + cells, was not significantly different between the KI + MW150 compared to KI + veh. ( n = 11 KI + veh; n = 14 KI + MW150). Data are mean ± SEM. Source data is available in Additional file : Table S3

Article Snippet: Fig. 6 Effect of MW150 treatment on microglia closely associated with Aβ plaques and microglia-internalized Aβ in the cortex of APP/PS1 KI mice. a Representative images of Imaris 3D reconstruction of plaques.

Techniques: Generated, Staining