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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Telles-Longui, Milena [1] ; Mourelle, Danilo [1] ; Schowe, Natalia Mendes [2, 1] ; Cipolli, Gabriela Cabett [3] ; Malerba, Helena Nascimento [2, 1] ; Buck, Hudson Sousa [2, 4] ; Viel, Tania Araujo [3, 1]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Grad Course Pharmacol, Sao Paulo - Brazil
[2] Res Grp Neuropharmacol Aging, Sao Paulo - Brazil
[3] Univ Sao Paulo, Sch Arts Sci & Humanities, Sao Paulo - Brazil
[4] Santa Casa Sao Paulo Sch Med Sci, Dept Physiol Sci, Sao Paulo - Brazil
Total Affiliations: 4
Document type: Journal article
Source: British Journal of Pharmacology; v. 176, n. 17 JULY 2019.
Web of Science Citations: 0
Abstract

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. (AU)

FAPESP's process: 13/06935-1 - Assessment of changes in senile plaques and cholinergic markers in the brain of mice subjected to a model of neurodegeneration after training attention
Grantee:Gabriela Cabett Cipolli
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 16/20574-0 - Treatment effectiveness evaluation with microdosing lithium, combined or not with enriched environment, for healthy aging
Grantee:Helena Nascimento Malerba
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 12/12917-3 - Evaluation of molecular changes in the brain cholinergic system after the use of non-pharmacological strategies to improve memory
Grantee:Tânia Araújo Viel
Support type: Regular Research Grants
FAPESP's process: 11/07365-9 - Role of alpha7 nicotinic cholinergic receptors in memory retention of mice submitted to neurodegeneration
Grantee:Milena Telles
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 16/07115-6 - Translational study of strategies and biomarkers to promote healthspan
Grantee:Tânia Araújo Viel
Support type: Regular Research Grants