Spatial Memory Training Counteracts Hippocampal GIRK Channel Decrease in the Transgenic APPSw,Ind J9 Alzheimer's Disease Mouse Model
Temprano-Carazo, Sara (Universidad de Castilla-La Mancha)
Contreras, Ana (Universidad de Castilla-La Mancha)
Saura Antolín, Carlos (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Navarro-López, Juan D. (Universidad de Castilla-La Mancha)
Jiménez-Díaz, Lydia (Universidad de Castilla-La Mancha)

Date:	2022
Abstract:	G-protein-gated inwardly rectifying potassium (GIRK) channels are critical determinants of neuronal excitability. They have been proposed as potential targets to restore excitatory/inhibitory balance in acute amyloidosis models, where hyperexcitability is a hallmark. However, the role of GIRK signaling in transgenic mice models of Alzheimer's disease (AD) is largely unknown. Here, we study whether progressive amyloid-β (Aβ) accumulation in the hippocampus during aging alters GIRK channel expression in mutant β-amyloid precursor protein (APP J9) transgenic AD mice. Additionally, we examine the impact of spatial memory training in a hippocampal-dependent task, on protein expression of GIRK subunits and Regulator of G-protein signaling 7 (RGS7) in the hippocampus of APP J9 mice. Firstly, we found a reduction in GIRK2 expression (the main neuronal GIRK channels subunit) in the hippocampus of 6-month-old APP J9 mice. Moreover, we found an aging effect on GIRK2 and GIRK3 subunits in both wild type (WT) and APP J9 mice. Finally, when 6-month-old animals were challenged to a spatial memory training, GIRK2 expression in the APP J9 mice were normalized to WT levels. Together, our results support the evidence that GIRK2 could account for the excitatory/inhibitory neurotransmission imbalance found in AD models, and training in a cognitive hippocampal dependent task may have therapeutic benefits of reversing this effect and lessen early AD deficits.
Grants:	Agencia Estatal de Investigación PID2019-106615RB-I00 Ministerio de Sanidad y Consumo CB06/05/0042
Note:	This work was supported by grants BFU2017-82494-P, PID2020-115823-GB100 funded by MCIN/AEI/10.13039/501100011033, and SBPLY/21/180501/000150 funded by JCCM and ERDF A way of making Europe, to LJD and JDNL; and grant PID2019-106615RB-I00 and Instituto de Salud Carlos III (CIBERNED CB06/05/0042) to CAS. AC held a Margarita Salas Postdoctoral Research Fellow funded by European Union NextGenerationEU/PRTR.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	International journal of molecular sciences, Vol. 23 Núm. 21 (november 2022) , p. 13444, ISSN 1422-0067

DOI: 10.3390/ijms232113444
PMID: 36362230

10 p, 1.8 MB

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