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?7 nicotinic ACh receptors are necessary for memory recovery and neuroprotection promoted by attention training in amyloid-?-infused mice.

ABSTRACT: BACKGROUND AND PURPOSE:Attention training reverses the neurodegeneration and memory loss promoted by infusion of amyloid-? (A?) peptide in rats and increases the density of ?7 nicotinic ACh receptors (?7nAChRs) in brain areas related to memory. Hence, we aimed to assess the role of ?7nAChRs in the memory recovery promoted by attention training. EXPERIMENTAL APPROACH:C57Bl/6 mice were chronically infused with A?, A? plus the ?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? caused cognitive impairment, which was reversed by the weekly training, whereas A? + 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? 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 ?7nAChR function leads to a loss of neuroprotection mechanisms. CONCLUSIONS AND IMPLICATIONS:The ?7nAChR has a determinant role in memory recovery and brain resilience in the presence of neurodegeneration promoted by A? peptide. These data support further studies concerning these receptors as pharmacological targets for future therapies.

SUBMITTER: Telles-Longui M

PROVIDER: S-EPMC6692581 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Telles-Longui Milena M Mourelle Danilo D Schöwe Natalia Mendes NM Cipolli Gabriela Cabett GC Malerba Helena Nascimento HN Buck Hudson Sousa HS Viel Tania Araujo TA

British journal of pharmacology 20190714 17

<h4>Background and purpose</h4>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.<h4>Experimental approach</h4>C57Bl/6 mice were chronically infused with Aβ, Aβ plus the α7 antagonist methyllycaconitine (MLA), or MLA alone. Con ...[more]

PMID: 31144293

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Project description:BackgroundAlthough evidence suggests that the prevalence of Parkinson's disease (PD) is lower in smokers than in non-smokers, the mechanisms of nicotine-induced neuroprotection remain unclear. Stimulation of the α7 nicotinic acetylcholine receptor (α7-nAChR) seems to be a crucial mechanism underlying the anti-inflammatory potential of cholinergic agonists in immune cells, including astrocytes, and inhibition of astrocyte activation has been proposed as a novel strategy for the treatment of neurodegenerative disorders such as PD. The objective of the present study was to determine whether nicotine-induced neuroprotection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model occurs via α7-nAChR-mediated inhibition of astrocytes.MethodsBoth in vivo (MPTP) and in vitro (1-methyl-4-phenylpyridinium ion (MPP+) and lipopolysaccharide (LPS)) models of PD were used to investigate the role(s) of and possible mechanism(s) by which α7-nAChRs protect against dopaminergic neuron loss. Multiple experimental approaches, including behavioral tests, immunochemistry, and stereology experiments, astrocyte cell cultures, reverse transcriptase PCR, laser scanning confocal microscopy, tumor necrosis factor (TNF)-α assays, and western blotting, were used to elucidate the mechanisms of the α7-nAChR-mediated neuroprotection.ResultsSystemic administration of nicotine alleviated MPTP-induced behavioral symptoms, improved motor coordination, and protected against dopaminergic neuron loss and the activation of astrocytes and microglia in the substantia nigra. The protective effects of nicotine were abolished by administration of the α7-nAChR-selective antagonist methyllycaconitine (MLA). In primary cultured mouse astrocytes, pretreatment with nicotine suppressed MPP(+)-induced or LPS-induced astrocyte activation, as evidenced by both decreased production of TNF-α and inhibition of extracellular regulated kinase1/2 (Erk1/2) and p38 activation in astrocytes, and these effects were also reversed by MLA.ConclusionTaken together, our results suggest that α7-nAChR-mediated inhibition of astrocyte activation is an important mechanism underlying the protective effects of nicotine.

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?7 nicotinic ACh receptors are necessary for memory recovery and neuroprotection promoted by attention training in amyloid-?-infused mice.

Publications

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

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