1. GM1 decreases neuropathology and weight loss in R6/2 mice
GM1 decreases neuropathology and weight loss in R6/2 mice Six‐week‐old mice were infused with GM1 or artificial cerebro‐spinal fluid (CSF, vehicle) for 28 days. Analysis was performed at the end of treatment (10 weeks of age). Striatal volume in the brain left hemisphere (LH, contralateral to infusion site). N = 13 WT CSF, 11 WT GM1, 11 R6/2 CSF, 9 R6/2 GM1.Number of neurons (NeuN+ cells) in the LH striatum between bregma 0.02 mm and −2.3 mm. N = 8 WT CSF, 5 WT GM1, 7 R6/2 CSF, 6 R6/2 GM1.Volume of the brain (LH) from bregma 2.1 mm to −2.3 mm. N = 13 WT CSF, 11 WT GM1, 11 R6/2 CSF, 9 R6/2 GM1.Time course of brain weight loss in R6/2 mice. N = 3 6‐week R6/2, 10 8‐week R6/2, 14 10‐week R6/2 CSF and 10 10‐week R6/2 GM1.Corpus callosum volume (LH) between bregma 2.1 mm and 0.02 mm. N = 13 WT CSF, 11 WT GM1, 11 R6/2 CSF, 9 R6/2 GM1.Total white matter tract volume in the striatum, from 0.02 mm to bregma to −1.06 mm. N = 13 WT CSF, 11 WT GM1, 11 R6/2 CSF, 9 R6/2 GM1.Representative microscopy images of the striatum after immunostaining with anti‐ferritin antibodies. Scale bars are 0.62 mm in length. Quantification of the immunoreactive area is shown in the graph. Eight serial sections were analysed and averaged for each mouse. N = 3 WT CSF, 4 WT GM1, 6 R6/2 CSF, 5 R6/2 GM1.Percent change in body weight at day 21 of treatment compared to baseline (day 0). N = 23 WT CSF, 21 WT GM1, 14 R6/2 CSF, 11 R6/2 GM1.Survival curve for R6/2 mice treated with CSF (N = 6) or GM1 (N = 5). X‐axis shows days after the beginning of GM1 treatment. The horizontal red line indicates the duration of GM1 treatment.Data information: Box‐and‐whisker plots show median, maximum and minimum values. Two‐way ANOVA with Holm–Sidak post‐test was used in (A–C and E–H); one‐way ANOVA with Tukey's post‐test in (D); log‐rank analysis was used in (I). *P < 0.05, **P < 0.01, ***P < 0.001.
Melanie Alpaugh et al. EMBO Mol Med. 2017;emmm
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