A cannabinoid link between mitochondria and memory

Autor: Gabriel Barreda-Gómez, Leire Reguero, Tifany Desprez, Marjorie Varilh, Jean-William Dupuy, Geoffrey Terral, Filippo Drago, Pedro Grandes, Roman Serrat, Michelangelo Colavita, Wilfrid Mazier, Nagore Puente, Giovanni Marsicano, M. Dolores García-Fernández, Edgar Soria-Gomez, Arnau Busquets-Garcia, Giovanni Benard, Antonio C Pagano Zottola, Anna Delamarre, Luigi Bellocchio, Maria-Luz Lopez-Rodriguez, Peggy Vincent, Izaskun Elezgarai, Daniela Cota, Federico Massa, Etienne Hebert-Chatelain, Astrid Cannich, Laurie M. Robin
Přispěvatelé: Department of Biology [Moncton], Université de Moncton, Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), CIBER de Enfermedades Neurodegenerativas (CIBERNED), Université de Bordeaux (UB), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Institut National de la Santé et de la Recherche Médicale (INSERM), Systèmes d'élevage, nutrition animale et humaine (SENAH), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Department of Clinical and Molecular Biomedicine, Università degli studi di Catania [Catania], University of the Basque Country [Bizkaia] (UPV/EHU), Centre Génomique Fonctionnelle Bordeaux [Bordeaux] (CGFB), Institut Polytechnique de Bordeaux-Université de Bordeaux Ségalen [Bordeaux 2], U1211 Laboratoire Maladies Rares: Génétique et Métabolisme, Maladies Rares - Génétique et Métabolisme (MRGM), Université Bordeaux Segalen - Bordeaux 2-Hôpital Pellegrin-Service de Génétique Médicale du CHU de Bordeaux, Laboratoire Maladies Rares : Génétique et Métabolisme [Bordeaux] (MRGM), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Cannabinoid receptor
medicine.medical_treatment
[SDV]Life Sciences [q-bio]
Cell Respiration
Molecular neuroscience
Mitochondrion
Biology
GTP-Binding Protein alpha Subunits
Gi-Go
Hippocampus
Synaptic Transmission
Oxidative Phosphorylation
Electron Transport
03 medical and health sciences
Mice
0302 clinical medicine
Receptor
Cannabinoid
CB1
Memory
medicine
Animals
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
Receptor
Protein kinase A
ComputingMilieux_MISCELLANEOUS
Memory Disorders
Multidisciplinary
Cannabinoids
NDUFS2
NADH Dehydrogenase
Cyclic AMP-Dependent Protein Kinases
Cell biology
Mitochondria
030104 developmental biology
Mitochondrial Membranes
Female
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Cannabinoid
Signal transduction
Energy Metabolism
030217 neurology & neurosurgery
Adenylyl Cyclases
Signal Transduction
Zdroj: Nature
Nature, Nature Publishing Group, 2016, 539 (7630), pp.555-559. ⟨10.1038/nature20127⟩
ISSN: 0028-0836
1476-4679
DOI: 10.1038/nature20127⟩
Popis: Cellular activity in the brain depends on the high energetic support provided by mitochondria, the cell organelles which use energy sources to generate ATP. Acute cannabinoid intoxication induces amnesia in humans and animals, and the activation of type-1 cannabinoid receptors present at brain mitochondria membranes (mtCB1) can directly alter mitochondrial energetic activity. Although the pathological impact of chronic mitochondrial dysfunctions in the brain is well established, the involvement of acute modulation of mitochondrial activity in high brain functions, including learning and memory, is unknown. Here, we show that acute cannabinoid-induced memory impairment in mice requires activation of hippocampal mtCB1 receptors. Genetic exclusion of CB1 receptors from hippocampal mitochondria prevents cannabinoid-induced reduction of mitochondrial mobility, synaptic transmission and memory formation. mtCB1 receptors signal through intra-mitochondrial Gαi protein activation and consequent inhibition of soluble-adenylyl cyclase (sAC). The resulting inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system eventually leads to decreased cellular respiration. Hippocampal inhibition of sAC activity or manipulation of intra-mitochondrial PKA signalling or phosphorylation of the Complex I subunit NDUFS2 inhibit bioenergetic and amnesic effects of cannabinoids. Thus, the G protein-coupled mtCB1 receptors regulate memory processes via modulation of mitochondrial energy metabolism. By directly linking mitochondrial activity to memory formation, these data reveal that bioenergetic processes are primary acute regulators of cognitive functions.
Databáze: OpenAIRE
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