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Fig. 2 | Acta Neuropathologica Communications

Fig. 2

From: Upregulating β-hexosaminidase activity in rodents prevents α-synuclein lipid associations and protects dopaminergic neurons from α-synuclein-mediated neurotoxicity

Fig. 2

AAV6-expressed HEX subunits A and B localize to lysosomes and boost enzymatic activity in the rat substantia nigra. a Adult rats received unilateral SNpc injections of AAV6s expressing either aSYN and a control vector, or aSYN+HEX subunits A and B. Biochemical and histological measurements were collected at 12 weeks post-injection, and comparisons were made between injected- and non-injected control hemispheres for each animal. b HEX activity histochemical detection assay (red precipitate) in a rat injected with AAV6s expressing HEX subunits A and B. (SNr = substantia nigra pars reticulata, VTA = ventral tegmental area). Boxed inserts are shown in higher magnification below. c Lysosomal HEX activity measured by artificial 4-MU-substrate in dissected SN from rats injected with CTRL+aSYN (n = 4) and HEX+aSYN (n = 2) (****:p < 0.0001, two-tailed t-test). d HPLC measurements of GM3 in spot-dissected ventral midbrain from control+aSYN and HEX+aSYN injected rats, normalized by the non-injected hemispheres (n = 4 / group). e Representative immunofluorescent micrograph showing AAV6-overexpressed human WT aSYN (magenta) in dopaminergic neurons (TH+) (green) in the rat striatum and SNpc. f Quantifications of # HEX A+ puncta / TH+ cell in images as in SFIG. 3 (n = 4 / group) (*:p < 0.05, Welch’s t-test)

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