Inhibition of calpains improves memory and synaptic transmission in a mouse model of Alzheimer disease
J. Clin. Invest. Fabrizio Trinchese, et al. 118:2796 doi:10.1172/JCI34254 [Go to this article.]

Figure 3
Calpain inhibition reestablished normal synaptic function following Aβ elevation. (A) E64 improved BST at the CA3-CA1 connection of hippocampal slices from 7-month-old APP/PS1 mice treated for 5 months (10 slices from 9 E64-treated APP/PS1 mice, 7 slices from 7 vehicle-treated APP/PS1 mice, 8 slices from 8 vehicle-treated WT mice; P < 0.01 comparing E64- and vehicle-treated APP/PS1 slices with 2-way ANOVA). BST was not affected in E64-treated WT animals (6 slices from 6 mice; P > 0.05). (B) BDA-410 reestablished normal BST in APP/PS1 mice treated with inhibitor between 8 weeks and 7 months of age (7 slices from 7 BDA-410–treated APP/PS1 mice, 9 slices from 8 vehicle-treated APP/PS1 mice, 8 slices from 7 vehicle-treated WT mice; P < 0.01 comparing BDA-410– and vehicle-treated APP/PS1 slices). BDA-410 did not affect BST in WT littermates (11 slices from 9 mice; P > 0.05). (C) E64 was beneficial against LTP impairment at the same synapses as in A (vehicle-treated APP/PS1 mice versus vehicle-treated WT mice, P < 0.01 with 2-way ANOVA; E64-treated APP/PS1 mice versus vehicle-treated APP/PS1 mice, P < 0.01). The inhibitor did not affect LTP in WT mice (P > 0.05). (D) BDA-410 reestablished normal LTP in APP/PS1 mice treated between 8 weeks and 7 months of age (BDA-410–treated APP/PS1 mice versus vehicle-treated APP/PS1 mice; P < 0.01; same synapses as in B). BDA-410 did not affect LTP in WT littermates (P > 0.05). (E) BDA-410 reestablished normal LTP in APP mice treated between 8 and 11 to 12 months of age (P < 0.05 in 6 slices from 6 BDA-410–treated APP mice versus 7 slices from 7 vehicle-treated APP mice; 7 slices from 7 vehicle-treated WT littermates). BDA-410 did not affect LTP in slices from WT littermates (7 slices from 7 mice; P > 0.05). BST did not vary among the 4 groups of mice (data not shown). (F) BDA-410 reestablished normal LTP in Aβ₄₂-perfused slices (6 slices treated with BDA-410 plus Aβ versus 8 Aβ-treated slices, P < 0.05; 6 vehicle-treated slices versus 7 BDA-410–treated slices). The bar indicates the perfusion with Aβ42.