Fig. 4: Lithium deficiency activates microglia and impairs Aβ clearance.
From: Lithium deficiency and the onset of Alzheimer’s disease
a, GO analysis of DEGs shared between Li-deficient (DEF) 3xTg (treatment from 5 to 9 months of age; n = 4 mice per group) and wild-type (WT; treatment from 12 to 20 months of age; n = 4 per group) microglia. b,c, 3xTg mice were fed a DEF or CTRL diet for either 5 weeks (starting at 10.8 months of age; n = 8 per group) or 9 months (starting at 6 months of age; n = 7 per group). Immunolabelling (b, left) of total (Iba1) and activated (CD68) microglia in the hippocampus (9-month treatment). Quantification of CD68+ cell density (b, right) and GPNMB and LPL microglial expression (c) in the hippocampus. d, Cytokine levels in culture medium of primary cortical microglia isolated from WT mice on CTRL or DEF diets from 12 to 18 months of age (n = 3 per group), after stimulation with 50 ng ml−1 LPS. Signals were normalized to internal controls from the cytokine array. Data are mean ± s.d. a.u., arbitrary units. e, Aβ42 uptake (left) and degradation (right) by primary cortical microglia isolated from 18-month-old WT mice after 6 months on CTRL or DEF diets (n = 3 per group). f, Immunolabelling (left) and quantification (right) of GSK3β in Iba1+ microglia in the hippocampus of 3xTg mice after 9 months on CTRL or DEF diets (n = 7 per group). g, Aβ42 uptake (left) and degradation (right) by primary microglia isolated from WT mice fed CTRL or DEF diets from 12 to 16 months of age, and then incubated in culture with the GSK3β inhibitors CHIR99021 (CH) or PF-04802367 (PF) (n = 6 biological replicates per group). In b–g, data were normalized to the mean of CTRL groups. In b,c,e–g, box plots show individual values, median (line), box limits (25th and 75th percentiles) and whiskers (minimum and maximum). P values calculated by unpaired two-tailed t-tests (a–f) or two-way ANOVA with Tukey’s post-hoc test (g). Scale bars, 20 μm.
