Telles-Longui_2019_Br.J.Pharmacol_176_3193

BACKGROUND AND PURPOSE: Attention training reverses the neurodegeneration and memory loss promoted by infusion of amyloid-beta (Abeta) peptide in rats and increases the density of alpha7 nicotinic ACh receptors (alpha7nAChRs) in brain areas related to memory. Hence, we aimed to assess the role of alpha7nAChRs in the memory recovery promoted by attention training. EXPERIMENTAL APPROACH: C57Bl/6 mice were chronically infused with Abeta, Abeta plus the alpha7 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: Abeta caused cognitive impairment, which was reversed by the weekly training, whereas Abeta + 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 Abeta 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 alpha7nAChR function leads to a loss of neuroprotection mechanisms. CONCLUSIONS AND IMPLICATIONS: The alpha7nAChR has a determinant role in memory recovery and brain resilience in the presence of neurodegeneration promoted by Abeta peptide. These data support further studies concerning these receptors as pharmacological targets for future therapies.