Fig. 6: Nanolipid-delivered Cx43 blocker rescues neuropathy and cognitive decline in AD mouse model.

a Experimental protocol. b Barnes’ maze-acquisition trial. The total latency to the target hole, primary latency, and primary exploratory error were quantified. c Barnes’ maze-probe trial. Time spent in the target quadrant and the total distance were quantified. Statistical test: two-sided t test. d Novel object recognition test. Discrimination index and exploration time were quantified. Statistical test: two-sided t test. e Open field test. Distance and time spent in the center zone and the total distance were quantified. Statistical test: two-sided t test. For behavioral tests, N = 9 (WT TAT and WT TAT-CX43) or 13 (APP/PS1 TAT and APP/PS1 TAT-CX43) mice. f EtBr uptake of acute brain slices with IBA1 counterstaining. Microglial EtBr intensity quantified was normalized to the TAT@LNP control. Scale bar, 20 μm. N = 5 mice. Statistical test: one-way ANOVA. g D-serine level in acute brain slice supernatant normalized to TAT@LNP control. N = 5 mice. Statistical test: two-sided t test. h IL1β and TNFα levels in acute brain slices. N = 5 mice. Statistical test: two-sided t test. i IBA1 and Methoxy X04 staining. Scale bar, 50 μm. Hippocampal microglia number and the periplaque microglia number were quantified. N = 5 mice. Statistical test: two-sided t test. j Methoxy X04 staining in the hippocampus. Scale bar, 50 μm. Aβ plaque number and compact plaque percentage were quantified. N = 5 mice. Statistical test: two-sided t test. k RTN3 and Aβ staining. Scale bar, 10 μm. RTN3 + puncta number at different distances from the plaque was quantified. N = 45 and 42 plaques. Statistical test: two-way ANOVA. l MitoSox Red staining of hippocampal CA1 neuron. Scale bar, 50 μm. Quantified MitoSox intensity was normalized to WT. N = 5 mice. Statistical test: two-sided t test. m LTP experiment on acute hippocampal slices. n Representative field excitatory post-synaptic potential (fEPSP) before and after LTP induction. o fEPSP slope during recording. Statistical test: two-way ANOVA. p Normalized fEPSP slope post-LTP induction. For the LTP experiment, N = 8 experiments from 4 mice. Statistical test: two-sided t test. Dot plots show mean ± SEM, each data point, and p-value. Significance: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Source data are provided as a Source Data file.