Fig. 7: LJ2a and LJ3a prevent dendritic spine loss induced by Aβ oligomers in hippocampal primary cultures.
From: Genuine selective caspase-2 inhibition with new irreversible small peptidomimetics
Swiss mice hippocampal neurons (E18) were cultured for 3 weeks in microfluidic chambers (20,000 neurons/chamber). Then neurons were pre-treated, or not, for 1 h with the indicated concentration of LJ2a or LJ3a, and treated for 6 h with 100 nM of monomeric Aβ (Aβ mono) or 100 nM of Aβ1-42 oligomers ([Aβ]n) then fixed and permeabilized for (immuno)staining with anti-MAP2, Phalloidin, anti-actin F, and anti-Bassoon. Microfluidic chambers were analyzed by fluorescence microscopy by counting phalloidin clusters affixed to MAP2 and Bassoon on hippocampal dendrites. a Representative micrograph of triple stained dendrites after 6 h in the presence (lower panel, [Aβ]n) or absence (upper panel, Co.) of Aβ oligomers. b, c. Quantification of dendritic spines in hippocampal neurons treated with LJ2a (b) or LJ3a (c) as indicated. Both inhibitors show synaptoprotective effects at submicromolar concentration. Histograms represent means (±SD) of 3 independent experiments (****p value <0.0001).
