Fig. 5
Lack of oligodendroglial β-glucocerebrosidase is sufficient to induce neurodegeneration, astrogliosis and neuroinflammation in vivo, a, b Representative electron microscopy images from optic nerve sections of 6-month-old Gba1f/f and Gba1f/f::cre mice (a) and relative quantification of degenerated axons (b). Red arrowheads indicate myelin whorls; yellow arrowheads indicate electron-dense accumulated organelles (****, p < 0.0001; unpaired two-tailed Student’s t-test; n = 18 randomly selected fields from 3 mice for Gba1f/f and n = 24 Gba1f/f::cre from 3 mice). Scale bar = 2 μm. c, d Representative electron microscopy images from striatum sections of 6-month-old Gba1f/f and Gba1f/f::cre mice (c) and relative quantification of degenerated axons (d). Red asterisks indicate empty axons (*, p < 0.05; unpaired two-tailed Student’s t-test; n = 26 randomly selected fields from 3 mice for Gba1f/f and n = 56 Gba1f/f::cre from 3 mice). e, f Representative western blot (e) for neurofilament H (NF-H) and relative densitometric quantification (f) of total brain protein extracts from 6-month-old Gba1f/f and Gba1f/f::cre mice. β-actin (ACTB) was used as loading control (*, p < 0.05; unpaired two-tailed Mann–Whitney test; n = 4 mice). Error bars indicate s.e.m. g, h Representative western blot (g) for MAP2 and relative densitometric quantification (h) of total brain protein extracts from 6-month-old Gba1f/f and Gba1f/f::cre mice. β-actin (ACTB) was used as loading control (unpaired two-tailed Mann–Whitney test; n = 4 mice). Error bars indicate s.e.m. i Absolute levels of serum neurofilament light chain (NF-L) in 6-month-old mice (unpaired Welch’s test, n = 8 mice). j, k Representative immunofluorescence (j) and relative quantification (k) for GFAP in cerebellum sections from 6-month-old Gba1f/f and Gba1f/f::cre mice (*, p < 0.05; unpaired two-tailed Student’s t-test; n = 4 mice). Error bars indicate s.e.m. Scale bar = 100 μm. l, m Representative immunofluorescence for MBP and IBA1 in optic nerve sections from 6-month-old Gba1f/f and Gba1f/f::cre mice (l) and relative quantification of IBA1+ microglial cell density (m). Scale bar = 100 μm (*, p < 0.05; unpaired two-tailed Student’s t-test; n = 3 mice). Error bars indicate s.e.m