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Efficacy of THN201, a Combination of Donepezil and Mefloquine, to Reverse Neurocognitive Deficits in Alzheimer's Disease.
Front Neurosci. 2020; 14:563.FN

Abstract

Donepezil (DPZ) is an acetylcholinesterase inhibitor used in Alzheimer's disease to restore cognitive functions but is endowed with limited efficacy. Recent studies pointed out the implication of astroglial networks in cognitive processes, notably via astrocyte connexins (Cxs), proteins involved in gap junction intercellular communications. Hence, we investigated the impact on cognition of pharmacological or genetic modulations of those astrocyte Cxs during DPZ challenge in two rodent models of Alzheimer's disease-like memory deficits. We demonstrated that the Cx modulator mefloquine (MEF) significantly enhanced the procognitive effect of DPZ in both models. In parallel, we determined that MEF potentiated DPZ-induced release of acetylcholine in hippocampus. Finally, local genetic silencing of astrocyte Cxs in the hippocampus was also found to enhance the procognitive effect of DPZ, pointing out the importance of Cx-dependent astrocyte networks in memory processes.

Authors+Show Affiliations

Theranexus, Lyon, France.Theranexus, Lyon, France.Theranexus, Lyon, France.Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), CNRS, UPS, Université de Toulouse, Toulouse, France.Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), CNRS, UPS, Université de Toulouse, Toulouse, France.Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), CNRS, UPS, Université de Toulouse, Toulouse, France.Amylgen, Montferrier-sur-Lez, France.Amylgen, Montferrier-sur-Lez, France.Laboratory of Neurotherapies and NeuroModulation, Neuroscience Research Center (CRN), University of Lausanne, Lausanne, Switzerland. Laboratory of Neurotherapies and NeuroModulation, Department of Clinical Neuroscience (DNC), Lausanne University Hospital (CHUV), Lausanne, Switzerland.Theranexus, Lyon, France.Theranexus, Lyon, France.Theranexus, Lyon, France.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32612499

Citation

Droguerre, Marine, et al. "Efficacy of THN201, a Combination of Donepezil and Mefloquine, to Reverse Neurocognitive Deficits in Alzheimer's Disease." Frontiers in Neuroscience, vol. 14, 2020, p. 563.
Droguerre M, Duchêne A, Picoli C, et al. Efficacy of THN201, a Combination of Donepezil and Mefloquine, to Reverse Neurocognitive Deficits in Alzheimer's Disease. Front Neurosci. 2020;14:563.
Droguerre, M., Duchêne, A., Picoli, C., Portal, B., Lejards, C., Guiard, B. P., Meunier, J., Villard, V., Déglon, N., Hamon, M., Mouthon, F., & Charvériat, M. (2020). Efficacy of THN201, a Combination of Donepezil and Mefloquine, to Reverse Neurocognitive Deficits in Alzheimer's Disease. Frontiers in Neuroscience, 14, 563. https://doi.org/10.3389/fnins.2020.00563
Droguerre M, et al. Efficacy of THN201, a Combination of Donepezil and Mefloquine, to Reverse Neurocognitive Deficits in Alzheimer's Disease. Front Neurosci. 2020;14:563. PubMed PMID: 32612499.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy of THN201, a Combination of Donepezil and Mefloquine, to Reverse Neurocognitive Deficits in Alzheimer's Disease. AU - Droguerre,Marine, AU - Duchêne,Adeline, AU - Picoli,Christèle, AU - Portal,Benjamin, AU - Lejards,Camille, AU - Guiard,Bruno P, AU - Meunier,Johann, AU - Villard,Vanessa, AU - Déglon,Nicole, AU - Hamon,Michel, AU - Mouthon,Franck, AU - Charvériat,Mathieu, Y1 - 2020/06/16/ PY - 2020/03/23/received PY - 2020/05/07/accepted PY - 2020/7/3/entrez PY - 2020/7/3/pubmed PY - 2020/7/3/medline KW - Alzheimer’s disease KW - amyloid beta KW - astroglial networks KW - behavioral tests KW - connexin KW - donepezil KW - mefloquine SP - 563 EP - 563 JF - Frontiers in neuroscience JO - Front Neurosci VL - 14 N2 - Donepezil (DPZ) is an acetylcholinesterase inhibitor used in Alzheimer's disease to restore cognitive functions but is endowed with limited efficacy. Recent studies pointed out the implication of astroglial networks in cognitive processes, notably via astrocyte connexins (Cxs), proteins involved in gap junction intercellular communications. Hence, we investigated the impact on cognition of pharmacological or genetic modulations of those astrocyte Cxs during DPZ challenge in two rodent models of Alzheimer's disease-like memory deficits. We demonstrated that the Cx modulator mefloquine (MEF) significantly enhanced the procognitive effect of DPZ in both models. In parallel, we determined that MEF potentiated DPZ-induced release of acetylcholine in hippocampus. Finally, local genetic silencing of astrocyte Cxs in the hippocampus was also found to enhance the procognitive effect of DPZ, pointing out the importance of Cx-dependent astrocyte networks in memory processes. SN - 1662-4548 UR - https://www.unboundmedicine.com/medline/citation/32612499/Efficacy_of_THN201,_a_Combination_of_Donepezil_and_Mefloquine,_to_Reverse_Neurocognitive_Deficits_in_Alzheimer's_Disease L2 - https://doi.org/10.3389/fnins.2020.00563 DB - PRIME DP - Unbound Medicine ER -
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