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Fig. 3 | Molecular Neurodegeneration

Fig. 3

From: Early long-term administration of the CSF1R inhibitor PLX3397 ablates microglia and reduces accumulation of intraneuronal amyloid, neuritic plaque deposition and pre-fibrillar oligomers in 5XFAD mouse model of Alzheimer’s disease

Fig. 3

PLX3397 treatment reduces microglia, accumulation of intraneuronal amyloid and extracellular amyloid deposits in 5XFAD mice. a Area occupied by Iba1-positive microglia in the analyzed brains is increased by ~ 40%–90% in the regions of cortex, hippocampus and amygdala in 5XFAD mice compared to wild-type (p < 0.0001 denoted by ****). PLX3397 treatment eliminates ~ 99% of microglia in both wild-type and 5XFAD mice (p < 0.001 denoted by ***). Graph bars indicate mean ± SEM (n = 9/group). b Area fraction occupied by intraneuronal amyloid and extracellular amyloid deposits was quantified for the regions of cortex, hippocampus and amygdala independently. Long-term treatment with PLX3397 significantly prevented accumulation of the intraneuronal amyloid and nearly completely aborted formation of amyloid plaques in the cortex (p < 0.0001 denoted by ****). In the hippocampus, the accumulation of intraneuronal amyloid was significantly reduced (p < 0.024 denoted by *) as the formation of extracellular amyloid plaques (p < 0.05 denoted by *). In the amygdala region of the brains intraneuronal amyloid was reduced (p < 0.0002 denoted by ***) and formation of amyloid plaques was prevented (p < 0.003 denoted by **). Graph bars indicate mean ± SEM (n = 9/group). c Based on morphology and presence or absence of DAPI-positive core, extracellular amyloid was divided into neuritic or other types of plaques and quantified in brains. Treatment with PLX3397 significantly reduced area fraction occupied by neuritic plaques and other types of plaques (non-neuritic) in the cortex (p < 0.000005 denoted by *****), hippocampus (p < 0.005 denoted by **) and amygdala (p < 0.00001 denoted by ****). Graph bars indicate mean ± SEM (n = 12/group). d Size of amyloid plaques was quantified in three regions of brains. Treatment with PLX3397 significantly reduced the size of amyloid plaques in the cortex, hippocampus and amygdala (p < 0.000001, denoted by ******). Graph bars indicate mean ± SEM (n = 12/group and the total size of > 300 plaques/group were analyzed)

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Molecular Neurodegeneration

ISSN: 1750-1326