Fig. 2
From: Impaired cellular bioenergetics caused by GBA1 depletion sensitizes neurons to calcium overload
Levels of expression of glutamate receptors and massive accumulation of glycosylceramides are not responsible for increased sensitivity to glutamate in gba1+/− and gba1−/− neurons. a Expression of the glutamate receptors Grik2 and Grin2b in gba1+/+, gba1+/−, and gba1−/− mice brains was measured at the mRNA level by qPCR (shown as scatter plot, mean ± SEM, n = 3 brains per genotype). These data show that Grik2 mRNA was slightly higher in gba1+/− compared with the other genotypes, while Grin2b mRNA levels were decreased in gba1+/− and gba1−/− compared with gba1+/+, showing that the increased glutamate sensitivity is not attributable to increased glutamate receptor expression (One-way Anova, post-hoc Bonferroni, **p < 0.01). b Protein expression of the glutamate receptors Grik2 and Grin2b in gba1+/+, gba1+/−, and gba1−/− mice brains were measured by western blot (shown as scatter plot, mean ± SEM, n = 4–5 brains per genotype). These data show that the expression of these receptors was unchanged at the protein level (One-way Anova, post-hoc Bonferroni). c–m Analysis of lipidomics performed by mass spectrometry on lipids extracted from gba1+/+, gba1+/−, and gba1−/− brains (n = 3 brains per genotype, data represented as scatter plot and mean ± SEM). Glycosylceramide (d18:1) levels were increased in gba1−/− but not in gba1+/+ and gba1+/− brains (One-way Anova, post-hoc Bonferroni, ***p < 0.001) (c), suggesting that the enzyme activity produced by a single copy of GBA1 gene is sufficient to avoid substrate accumulation. Curiously, glycosylceramide (d18:0) levels were unchanged (d), as well as Cer, PC, lyso-PC, SM (e–h), while PE and PS are significantly changed in the disease models compared with wild-type brains (i–l)
