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Figure 4 | Acta Neuropathologica Communications

Figure 4

From: Reducing hippocampal extracellular matrix reverses early memory deficits in a mouse model of Alzheimer’s disease

Figure 4

ChABC treatment restores hippocampal memory and LTP in 3 months old APP/PS1 mice. a Contextual fear memory was tested in animals that received intra-hippocampal injections of either penicillinase (Pen) or chondroitinase ABC (ChABC) 24 h prior to the test. b Memory retrieval was significantly reduced in Pen treated APP/PS1 transgenic (TG) mice (n = 10) compared with Pen treated wildtype (WT) mice (n = 8). ChABC treatment rescued memory performance in APP/PS1 mice (n = 7) but had no effect in wildtype mice (n = 8) (genotype x treatment Two-Way ANOVA: F 1,30 = 4.41, p = 0.0442; mean ± SEM; ns, not significant; *p < 0.05). c WFA-staining confirmed a reduction in ECM levels due to injection of ChABC directly into the hippocampus. Dashed lines mark the hippocampal region that is affected by ChABC treatment. CA, cornus ammonis; DG, dentate gyrus. Scale bars: 400 μm. d LTP was induced in hippocampal slices obtained from Pen and ChABC treated APP/PS1 and wildtype mice. Single fEPSP traces before (grey) and after (black) tetanus stimulation are shown for each condition. Scale bars: 0.1 mV; 2 ms. e LTP was elicited in slices of Pen treated wildtype mice (n = 6), but not in slices of Pen treated APP/PS1 mice (n = 11). ChABC treatment partially rescued LTP in APP/PS1 mice (n = 7) but also slightly reduced LTP in wildtype mice (n = 3) (mean ± SEM). f Statistical analysis of the average fEPSP change at 10–20 min showed a significant LTP impairment in Pen treated APP/PS1 mice compared with Pen treated wildtype mice, and a significant LTP rescue in ChABC treated APP/PS1 mice compared with Pen treated APP/PS1 mice (genotype x treatment Two-Way ANOVA: F 1,23 = 6.87, p = 0.0153; mean ± SEM; ns, not significant; **p < 0.01).

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