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Fig. 6 | Molecular Neurodegeneration

Fig. 6

From: Caspase vinyl sulfone small molecule inhibitors prevent axonal degeneration in human neurons and reverse cognitive impairment in Caspase-6-overexpressing mice

Fig. 6

Hippocampal levels of synaptic and glial markers are unchanged with NWL-117 treatment. a Levels of Casp6 p20p10 (Casp6p20p10), α-tubulin-cleaved by Casp6 (TubΔCasp6), α-tubulin (Tubulin), and β-actin in hippocampal protein extracts WT/WT, WT/Cre, and KI/Cre mice treated with saline or 20 mg/Kg NWL-117. b & c Immunohistochemistry of TubΔCasp6-stained hippocampi from KI/Cre mice treated with saline (b) or NWL-117 (c). Arrowheads mark some positive immunoreactivity. d Quantification of positive immunostaining shown in panel (b) and (c). e Levels of p97 and p97-cleaved by Casp6 (p97ΔCasp6) in hippocampal protein extracts of KI/Cre mice treated with saline (n = 3) or NWL-117 (n = 3). f Quantification of the levels of p97ΔCasp6/p97 shown in panel (e). g & h Levels of synapsin in hippocampal extracts from KI/Cre mice treated with saline (n = 3) or NWL-117 (n = 3) (g) and quantified in (h). i Levels of Synaptophysin in hippocampal protein extracts from WT/WT, WT/Cre, and KI/Cre (Casp6 overexpressing) mice treated with saline or NWL-117. j–k Brightfield scans of KI/Cre-Saline (j) and NWL-117 (k) mice brains stained for synaptophysin by immunohistochemistry and quantification (l). m & n Iba1-stained hippocampi from KI/Cre mice treated with saline (m) or NWL-117 (n). Arrowheads mark some positive immunoreactivity. o Quantification of the area of positive immunostaining for Iba1 over the total area of the tissue. p Levels of GFAP in hippocampal extracts from KI/Cre mice treated with saline (n = 3) or NWL-117 (n = 3). q Quantification of the levels of GFAP/β-actin. For panels (d), (l), and (o), data represent the mean ± SEM for each group: Control-saline (n = 5), Control-NWL-117 (n = 5), KI/Cre-saline (n = 5), and KI/Cre-NWL-117 (n = 4). Statistical analysis was performed by two-way ANOVA and no significant differences were found. For panels (f), (h), and (q), data represent the mean ± SEM and statistical analysis was performed by unpaired two-tailed t test, no significant differences were found. SO: Stratum Oriens, PCL: Pyramidal Cell layer, SR: Stratum Radiatum, SLM: Stratum Lacunosum

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