Conclusions
Tc1 mice present several toxicity markers similar to those observed in amyloid-β [25-35] peptide-treated wildtype mice, suggesting that developmental modifications in these mice modify their response to amyloid peptide. However, amyloid toxicity led to severe memory deficits in this Down syndrome mouse model.
Results
Intracerebroventricular injection of oligomeric amyloid-β [25-35] peptide in three-month-old wildtype mice induced learning deficits, oxidative stress, synaptic marker alterations, activation of glycogen synthase kinase-3β, inhibition of protein kinase B (AKT), and apoptotic pathways as compared to scrambled peptide-treated wildtype mice. Scrambled peptide-treated Tc1 mice presented high levels of toxicity markers as compared to wildtype mice. Amyloid-β [25-35] peptide injection in Tc1 mice induced significant learning deficits and enhanced glycogen synthase kinase-3β activity in the cortex and expression of apoptotic markers in the hippocampus and cortex. Interestingly, several markers, including oxidative stress, synaptic markers, glycogen synthase kinase-3β activity in the hippocampus and AKT activity in the hippocampus and cortex, were unaffected by amyloid-β [25-35] peptide injection in Tc1 mice. Conclusions: Tc1 mice present several toxicity markers similar to those observed in amyloid-β [25-35] peptide-treated wildtype mice, suggesting that developmental modifications in these mice modify their response to amyloid peptide. However, amyloid toxicity led to severe memory deficits in this Down syndrome mouse model.