α7 nicotinic ACh receptors are necessary for memory recovery and neuroprotection promoted by attention training in amyloid-β-infused mice

Background and Purpose Attention training reverses the neurodegeneration and memory loss promoted by infusion of amyloid-beta (A beta) peptide in rats and increases the density of alpha 7 nicotinic ACh receptors (alpha 7nAChRs) in brain areas related to memory. Hence, we aimed to assess the role of alpha 7nAChRs in the memory recovery promoted by attention training. Experimental Approach C57Bl/6 mice were chronically infused with A beta, A beta plus the alpha 7 antagonist methyllycaconitine (MLA), or MLA alone. Control animals were infused with vehicle. Animals were subjected weekly to the active avoidance shuttle box for 4 weeks (attention training). The brain and serum were collected for biochemical and histological analysis. Key Results A beta caused cognitive impairment, which was reversed by the weekly training, whereas A beta + MLA also promoted memory loss but with no reversal with weekly training. MLA alone also promoted memory loss but with only partial reversal with the training. Animals infused with A beta alone showed senile plaques in hippocampus, no change in BDNF levels in cortex, hippocampus, and serum, but increased AChE activity in cortex and hippocampus. Co-treatment with MLA increased AChE activity and senile plaque deposition in hippocampus as well as reducing BDNF in hippocampus and serum, suggesting a lack of alpha 7nAChR function leads to a loss of neuroprotection mechanisms. Conclusions and Implications The alpha 7nAChR has a determinant role in memory recovery and brain resilience in the presence of neurodegeneration promoted by A beta peptide. These data support further studies concerning these receptors as pharmacological targets for future therapies.