@article{10902/35284,
year = {2024},
url = {https://hdl.handle.net/10902/35284},
abstract = {A combination of  A9-tetrahydrocannabinol ( A9-THC) and cannabidiol (CBD) at non-psychoactive doses was previously demonstrated to reduce cognitive decline in APP/PS1 mice, an animal model of Alzheimer's disease (AD). However, the neurobiological substrates underlying these therapeutic properties of  A9-THC and CBD are not fully understood. Considering that dysregulation of glutamatergic activity contributes to cognitive impairment in AD, the present study evaluates the hypothesis that the combination of these two natural cannabinoids might reverse the alterations in glutamate dynamics within the hippocampus of this animal model of AD. Interestingly, our findings reveal that chronic treatment with  A9-THC and CBD, but not with any of them alone, reduces extracellular glutamate levels and the basal excitability of the hippocampus in APP/PS1 mice. These effects are not related to significant changes in the function and structure of glutamate synapses, as no relevant changes in synaptic plasticity, glutamate signaling or in the levels of key components of these synapses were observed in cannabinoid-treated mice. Our data instead indicate that these cannabinoid effects are associated with the control of glutamate uptake and/or to the regulation of the hippocampal network. Taken together, these results support the potential therapeutic properties of combining these natural cannabinoids against the excitotoxicity that occurs in AD brains.},
organization = {This study was supported by Ministerio de Ciencia, Innovacion y  Universidades–Agencia Estatal de Investigacion-FEDER funds/European Regional Development Fund – “a way to build Europe” grants RTI2018- 097773-A-I00 and PID2022-141123OB-I00 to EA, PID2020-118511RBI00 to FC, PID2020-119305RB-I00 to XG and PID2020-117989RA-I00 to JB, by Departament de Recerca i Universitats de la Generalitat de Catalunya (2021 SGR 00698) to FC and by CYTED-Programa Iberoamericano de Ciencia y Tecnología para el Desarrollo (P219RT0008) to EA. Founded by MCIN/AEI/10.13039/501100011033 “ESF Investing in your future” grant PRE2019-088153 to NSF and grant FPU19/03142 to LGA.},
publisher = {Elsevier},
publisher = {Neurotherapeutics, 2024, 21(5), e00439},
title = {A combination of A(9)-tetrahydrocannabinol and cannabidiol modulates glutamate dynamics in the hippocampus of an animal model of Alzheimer's disease},
author = {Sánchez Fernández, Nuria and Gómez Acero, Laura and Castañé, Anna and Adell Calduch, Albert and Campa, Leticia and Bonaventura, 
Jordi and Brito, Verónica and Ginés, Silvia and Queiróz, Francisco and Silva, Henrique and Lopes, João Pedro and Lopes, Cátia R. and Radoševic, Marija and Gasull, Xavier and Cunha, Rodrigo A. and Köfalvi, Attila and Ferreira, Samira G. and Ciruela, Francisco and Aso, Ester},
}