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bioRxiv · 10.1101/2022.05.20.492780

Spatial memory training reverses GirK channels modulation in the transgenic APPSw,Ind Alzheimer's disease mouse model

Temprano-Carazo, S.·Contreras, A.·Saura, C. A.·Navarro-Lopez, J. D.·Jimenez-Diaz, L.
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Abstract

Alzheimers disease (AD) is a dementia characterized by progressive memory decline and neurodegeneration caused by the accumulation of amyloid-{beta} (A{beta}) peptides. Last findings point to an imbalance between excitatory and inhibitory neurotransmission as the initial impairment in early stages, and the hippocampus as one of the most susceptible brain areas. The G-protein-gated inwardly rectifying potassium (GirK) channel has been proposed as a potential target to restore excitatory/inhibitory balance in amyloidosis models. Moreover, cognitive training may counteract early AD symptoms, although its effect on GirK channels remains unknown. Here, the effect of genotype, age, and training in a hippocampal-dependent memory task on the protein expression of GirK subunits and modulators were studied using APPSw,Ind mice. Results showed a reduction of GirK2 expression as well as an increased expression of SNX27 in the hippocampus of 6-month-old APPSw,Ind mice. Training in a memory task restored GirK2 and SNX27 levels. Thus, the effect of A{beta} on GirK2 could account for the excitatory/inhibitory imbalance transmission found in AD models, and training in a cognitive hippocampal-dependent task reverses this effect and lessens early A{beta}-dependent AD deficits. Summary statementA{beta} decreases hippocampal GirK2 expression in APPSw,Ind mice, which could contribute to early hyperexcitability found in Alzheimers disease models. Training in spatial memory tasks has shown to counteract this reduction.

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Temprano-Carazo, S., Contreras, A., Saura, C. A., Navarro-Lopez, J. D., Jimenez-Diaz, L.. 2022-05-20. Spatial memory training reverses GirK channels modulation in the transgenic APPSw,Ind Alzheimer's disease mouse model. https://doi.org/10.1101/2022.05.20.492780

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