Fig. 3

LDN/OSU-0215111 efficacy at moderate disease stage. a–d Results of behavioral battery (n = 27/27/23/27, respectively). Compound treatment normalized hyperactivity in the open field (a), short-term memory in the Y-maze (b), recognition memory in the NORT, (c) and cognition in the T-maze (d). e PSD-95 expression in hippocampal postsynaptic densities of rTg4510 was significantly reduced (n = 5/5/4/4, respectively), showing synaptic loss. Compound treatment in rTg4510 mice restored synaptic integrity indistinguishable from controls. f Hippocampal crude membrane preparations (n = 5/5/4/4, respectively) revealed increased EAAT2 in the rTg4510 vehicle group which was partially normalized by compound treatment. g Representative immunohistochemistry images of hippocampal subregions (n = 4 animals/group; average of ≥ 3 sections/animal). The cell nuclei were stained by DAPI (blue). Quantification (right) is percent change relative to control vehicle (dashed line), except MC1 (compared to rTg4510 vehicle). Control groups exhibited no differences. NeuN immunostaining demonstrated significant neurodegeneration in CA1 and DG of rTg4510 mice, which was prevented by compound treatment. Compound treatment maintained CA3 synaptic integrity (synaptophysin) and significantly reduced neurofibrillary tangle accumulation (MC1) in CA1 of rTg4510 mice. Finally, GFAP immunoreactivity was significantly increased in both rTg4510 groups, but compound treatment reduced gliosis. Scale bar = 100 μm. *P < 0.05, **P < 0.01, ***P < 0.001