Localization of the cannabinoid type-1 receptor in subcellular astrocyte compartments of mutant mouse hippocampus.
Glia. 2018-02-26; 66(7): 1417-1431
Lire sur PubMed
1. Glia. 2018 Jul;66(7):1417-1431. doi: 10.1002/glia.23314. Epub 2018 Feb 26.
Localization of the cannabinoid type-1 receptor in subcellular astrocyte
compartments of mutant mouse hippocampus.
Gutiérrez-Rodríguez A(1)(2), Bonilla-Del Río I(1)(2), Puente N(1)(2),
Gómez-Urquijo SM(1)(2), Fontaine CJ(3), Egaña-Huguet J(1)(2), Elezgarai I(1)(2),
Ruehle S(4), Lutz B(4), Robin LM(5)(6), Soria-Gómez E(1)(2), Bellocchio L(5)(6),
Padwal JD(7), van der Stelt M(7), Mendizabal-Zubiaga J(1)(2), Reguero L(1)(2),
Ramos A(1)(2), Gerrikagoitia I(1)(2), Marsicano G(5)(6), Grandes P(1)(2)(3).
(1)Department of Neurosciences, University of the Basque Country UPV/EHU, Leioa,
(2)Achucarro Basque Center for Neuroscience, Science Park of the UPV/EHU, Leioa,
(3)Division of Medical Sciences, University of Victoria, Victoria, British
Columbia, V8P 5C2, Canada.
(4)Institute of Physiological Chemistry and German Resilience Center, University
Medical Center of the Johannes Gutenberg University Mainz, Mainz, 55128, Germany.
(5)INSERM, U1215 Neurocentre Magendie, Endocannabinoids and Neuroadaptation,
Bordeaux, F-33077, France.
(6)Université de Bordeaux, Bordeaux, F-33077, France.
(7)Department of Molecular Physiology, Leiden University, Einsteinweg 55, Leiden,
CC, 2333, The Netherlands.
Astroglial type-1 cannabinoid (CB1 ) receptors are involved in synaptic
transmission, plasticity and behavior by interfering with the so-called
tripartite synapse formed by pre- and post-synaptic neuronal elements and
surrounding astrocyte processes. However, little is known concerning the
subcellular distribution of astroglial CB1 receptors. In particular, brain CB1
receptors are mostly localized at cells’ plasmalemma, but recent evidence
indicates their functional presence in mitochondrial membranes. Whether CB1
receptors are present in astroglial mitochondria has remained unknown. To
investigate this issue, we included conditional knock-out mice lacking astroglial
CB1 receptor expression specifically in glial fibrillary acidic protein
(GFAP)-containing astrocytes (GFAP-CB1 -KO mice) and also generated genetic
rescue mice to re-express CB1 receptors exclusively in astrocytes (GFAP-CB1 -RS).
To better identify astroglial structures by immunoelectron microscopy, global CB1
knock-out (CB1 -KO) mice and wild-type (CB1 -WT) littermates were
intra-hippocampally injected with an adeno-associated virus expressing humanized
renilla green fluorescent protein (hrGFP) under the control of human GFAP
promoter to generate GFAPhrGFP-CB1 -KO and -WT mice, respectively. Furthermore,
double immunogold (for CB1 ) and immunoperoxidase (for GFAP or hrGFP) revealed
that CB1 receptors are present in astroglial mitochondria from different
hippocampal regions of CB1 -WT, GFAP-CB1 -RS and GFAPhrGFP-CB1 -WT mice. Only
non-specific gold particles were detected in mouse hippocampi lacking CB1
receptors. Altogether, we demonstrated the existence of a precise molecular
architecture of the CB1 receptor in astrocytes that will have to be taken into
account in evaluating the functional activity of cannabinergic signaling at the
© 2018 Wiley Periodicals, Inc.