Frontiers in Neuroanatomy (Oct 2022)
Up-regulation of CB1 cannabinoid receptors located at glutamatergic terminals in the medial prefrontal cortex of the obese Zucker rat
- Leyre Echeazarra,
- Leyre Echeazarra,
- Sergio Barrondo,
- Sergio Barrondo,
- Sergio Barrondo,
- Gontzal García del Caño,
- Gontzal García del Caño,
- Itziar Bonilla-Del Río,
- Itziar Bonilla-Del Río,
- Jon Egaña-Huguet,
- Jon Egaña-Huguet,
- Nagore Puente,
- Nagore Puente,
- Xabier Aretxabala,
- Mario Montaña,
- Maider López de Jesús,
- Maider López de Jesús,
- Imanol González-Burguera,
- Imanol González-Burguera,
- Miquel Saumell-Esnaola,
- Miquel Saumell-Esnaola,
- María Aránzazu Goicolea,
- Pedro Grandes,
- Pedro Grandes,
- Pedro Grandes,
- Joan Sallés,
- Joan Sallés,
- Joan Sallés
Affiliations
- Leyre Echeazarra
- Department of Physiology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain
- Leyre Echeazarra
- Bioaraba, Dispositivos Móviles para el Control de Enfermedades Crónicas, Vitoria-Gasteiz, Spain
- Sergio Barrondo
- Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain
- Sergio Barrondo
- Centro de Investigación Biomédica en Red de Salud Mental, Madrid, Spain
- Sergio Barrondo
- Bioaraba, Neurofarmacología Celular y Molecular, Vitoria-Gasteiz, Spain
- Gontzal García del Caño
- Bioaraba, Neurofarmacología Celular y Molecular, Vitoria-Gasteiz, Spain
- Gontzal García del Caño
- Department of Neurosciences, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain
- Itziar Bonilla-Del Río
- Department of Neurosciences, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
- Itziar Bonilla-Del Río
- Achucarro Basque Center for Neuroscience, Science Park of the University of the Basque Country (UPV/EHU), Leioa, Spain
- Jon Egaña-Huguet
- Department of Neurosciences, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
- Jon Egaña-Huguet
- Achucarro Basque Center for Neuroscience, Science Park of the University of the Basque Country (UPV/EHU), Leioa, Spain
- Nagore Puente
- Department of Neurosciences, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
- Nagore Puente
- Achucarro Basque Center for Neuroscience, Science Park of the University of the Basque Country (UPV/EHU), Leioa, Spain
- Xabier Aretxabala
- Department of Neurosciences, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain
- Mario Montaña
- Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain
- Maider López de Jesús
- Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain
- Maider López de Jesús
- Bioaraba, Neurofarmacología Celular y Molecular, Vitoria-Gasteiz, Spain
- Imanol González-Burguera
- Bioaraba, Neurofarmacología Celular y Molecular, Vitoria-Gasteiz, Spain
- Imanol González-Burguera
- Department of Neurosciences, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain
- Miquel Saumell-Esnaola
- Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain
- Miquel Saumell-Esnaola
- Bioaraba, Neurofarmacología Celular y Molecular, Vitoria-Gasteiz, Spain
- María Aránzazu Goicolea
- Department of Analytical Chemistry, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain
- Pedro Grandes
- Department of Neurosciences, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
- Pedro Grandes
- Achucarro Basque Center for Neuroscience, Science Park of the University of the Basque Country (UPV/EHU), Leioa, Spain
- Pedro Grandes
- 0Division of Medical Sciences, University of Victoria, Victoria, BC, Canada
- Joan Sallés
- Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain
- Joan Sallés
- Centro de Investigación Biomédica en Red de Salud Mental, Madrid, Spain
- Joan Sallés
- Bioaraba, Neurofarmacología Celular y Molecular, Vitoria-Gasteiz, Spain
- DOI
- https://doi.org/10.3389/fnana.2022.1004702
- Journal volume & issue
-
Vol. 16
Abstract
The present study describes a detailed neuroanatomical distribution map of the cannabinoid type 1 (CB1) receptor, along with the biochemical characterization of the expression and functional coupling to their cognate Gi/o proteins in the medial prefrontal cortex (mPCx) of the obese Zucker rats. The CB1 receptor density was higher in the prelimbic (PL) and infralimbic (IL) subregions of the mPCx of obese Zucker rats relative to their lean littermates which was associated with a higher percentage of CB1 receptor immunopositive excitatory presynaptic terminals in PL and IL. Also, a higher expression of CB1 receptors and WIN55,212-2-stimulated [35S]GTPγS binding was observed in the mPCx but not in the neocortex (NCx) and hippocampus of obese rats. Low-frequency stimulation in layers II/III of the mPCx induced CB1 receptor-dependent long-term synaptic plasticity in IL of area obese Zucker but not lean rats. Overall, the elevated 2-AG levels, up-regulation of CB1 receptors, and increased agonist-stimulated [35S]GTPγS binding strongly suggest that hyperactivity of the endocannabinoid signaling takes place at the glutamatergic terminals of the mPCx in the obese Zucker rat. These findings could endorse the importance of the CB1 receptors located in the mPCx in the development of obesity in Zucker rats.
Keywords
- obese Zucker rat
- CB1 receptor
- Gi/o proteins
- 2-AG levels
- medial prefrontal cortex
- glutamatergic terminals
