Extended Data Fig. 9: Effect of CMA activation on synaptic density, long-term memory and seizure susceptibility.
a–h, Representative images (a,e) and quantification of PSD95+vGluT1+ puncta (b–d) and Homer1+SV2+ puncta (f–h) in stratum radiatum in hippocampus of young (Y, 4–6 months old) h2AOE and control (Ctrl) female and male mice. Scale bars: 50 μm (lower magnification panels) or 10 μm (insets). i–k, Quantification of seizure severity (i), frequency (j) and duration (k) following PTZ (40mg kg−1) injection in 4–6 months old female and male hL2AOE and Ctrl mice. l,m, Long-term memory quantified in the novel-arm Y-maze test as percentage of entries made (right panels) or percentage of time spent (left panels) in novel arm in young (6 months) or old (23 months) female (l) and male (m) mice that received CA77.1 or vehicle 4 months prior to the memory assessment. n, Representative full field images of immunostaining for Dendra, LAMP1 (L1), and human Tau (hTau) in hippocampal CA1 pyramidal neurons from 4 months old male KFERQDendra; ×3TG (expressing APPSwe, PS2N141I, and hTauP301L), and quantification of KFERQDendra+LAMP1+ and LAMP1+ puncta separately in female and mice as fold of sex-matched controls in the same images. Scale bar: 50 μm. o, Quantification of seizure duration (left) or severity (right) following PTZ (40 mg kg−1) injection in 6 months old females (open triangles) and males (closed circles) ×3TG mice, 2 months after daily administration of CA77.1 or vehicle (Veh.). The doted lines in n indicate no changes relative to control (x3TG/Ctrl = 1). From left to right in each group: n = [4 Ctrl females, 6 hL2AOE females, 4 Ctrl males, 5 hL2AOE males] (b–d,f–h), [7, 13] (i–k left), [16, 14] (i–k right), [9, 8, 7] (l), [5, 8, 9] (m), [4, 5] (n), [11, 5, 9] (o left), [16, 11, 12] (o right) mice. Two-tailed unpaired Student’s t-test (b–d,f–k,n), two-way ANOVA with Tukey’s multiple comparison test (l,m) or one-way ANOVA with Tukey’s multiple comparison test (o) are used. Data are presented as mean values ±SEM.
