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-β (Aβ) peptide in rats and increases the density of α7 nicotinic ACh receptors (α7nAChRs) in brain areas related to memory. Hence, we aimed to assess the role of α7nAChRs in the memory recovery promoted by attention training. EXPERIMENTAL APPROACH: C57Bl/6 mice were chronically infused with Aβ, Aβ plus the α7 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: Aβ caused cognitive impairment, which was reversed by the weekly training, whereas Aβ + 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 Aβ 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 α7nAChR function leads to a loss of neuroprotection mechanisms. CONCLUSIONS AND IMPLICATIONS: The α7nAChR has a determinant role in memory recovery and brain resilience in the presence of neurodegeneration promoted by Aβ peptide. These data support further studies concerning these receptors as pharmacological targets for future therapies.