CB₁ receptor activation inhibits neuronal and astrocytic intermediary metabolism in the rat hippocampus
Duarte, João M N LU
; Ferreira, Samira G
; Carvalho, Rui A.
; Cunha, Rodrigo A
and Köfalvi, Attila
(2012)
In Neurochemistry International
60(1).
p.1-8
- Abstract
Cannabinoid CB₁ receptor (CB₁R) activation decreases synaptic GABAergic and glutamatergic transmission and it also controls peripheral metabolism. Here we aimed at testing with ¹³C NMR isotopomer analysis whether CB₁Rs could have a local metabolic role in brain areas having high CB₁R density, such as the hippocampus. We labelled hippocampal slices with the tracers [2-¹³C]acetate, which is oxidized in glial cells, and [U-¹³C]glucose, which is metabolized both in glia and neurons, to evaluate metabolic compartmentation between glia and neurons. The synthetic CB₁R agonist WIN55212-2 (1 μM) significantly decreased the metabolism of both [2-¹³C]acetate (-11.6±2.0%) and [U-¹³C]glucose (-11.2±3.4%) in the tricarboxylic acid cycle that... (More)
Cannabinoid CB₁ receptor (CB₁R) activation decreases synaptic GABAergic and glutamatergic transmission and it also controls peripheral metabolism. Here we aimed at testing with ¹³C NMR isotopomer analysis whether CB₁Rs could have a local metabolic role in brain areas having high CB₁R density, such as the hippocampus. We labelled hippocampal slices with the tracers [2-¹³C]acetate, which is oxidized in glial cells, and [U-¹³C]glucose, which is metabolized both in glia and neurons, to evaluate metabolic compartmentation between glia and neurons. The synthetic CB₁R agonist WIN55212-2 (1 μM) significantly decreased the metabolism of both [2-¹³C]acetate (-11.6±2.0%) and [U-¹³C]glucose (-11.2±3.4%) in the tricarboxylic acid cycle that contributes to the glutamate pool. WIN55212-2 also significantly decreased the metabolism of [U-¹³C]glucose (-11.7±4.0%) but not that of [2-¹³C]acetate contributing to the pool of GABA. These effects of WIN55212-2 were prevented by the CB₁R antagonist AM251 (500 nM). These results thus suggest that CB₁Rs might be present also in hippocampal astrocytes besides their well-known neuronal localization. Indeed, confocal microscopy analysis revealed the presence of specific CB₁R immunoreactivity in astrocytes and pericytes throughout the hippocampus. In conclusion, CB₁Rs are able to control hippocampal intermediary metabolism in both neuronal and glial compartments, which suggests new alternative mechanisms by which CB₁Rs control cell physiology and afford neuroprotection.
(Less)
- author
- Duarte, João M N
LU
; Ferreira, Samira G
; Carvalho, Rui A.
; Cunha, Rodrigo A
and Köfalvi, Attila
- publishing date
- 2012-01
- type
- Contribution to journal
- publication status
- published
- keywords
- Animals, Astrocytes, Benzoxazines, Glucose, Glutamic Acid, Hippocampus, Magnetic Resonance Spectroscopy, Male, Morpholines, Naphthalenes, Neurons, Rats, Rats, Wistar, Receptor, Cannabinoid, CB1, Receptors, Drug, gamma-Aminobutyric Acid, Journal Article, Research Support, Non-U.S. Gov't
- in
- Neurochemistry International
- volume
- 60
- issue
- 1
- pages
- 8 pages
- publisher
- Elsevier
- external identifiers
-
- scopus:83455224661
- pmid:22085448
- ISSN
- 0197-0186
- DOI
- 10.1016/j.neuint.2011.10.019
- language
- English
- LU publication?
- no
- id
- 3f0c688b-3dd1-4a2a-9625-e75516f6fc70
- date added to LUP
- 2017-10-19 15:21:33
- date last changed
- 2025-11-26 02:22:44
@article{3f0c688b-3dd1-4a2a-9625-e75516f6fc70,
abstract = {{<p>Cannabinoid CB₁ receptor (CB₁R) activation decreases synaptic GABAergic and glutamatergic transmission and it also controls peripheral metabolism. Here we aimed at testing with ¹³C NMR isotopomer analysis whether CB₁Rs could have a local metabolic role in brain areas having high CB₁R density, such as the hippocampus. We labelled hippocampal slices with the tracers [2-¹³C]acetate, which is oxidized in glial cells, and [U-¹³C]glucose, which is metabolized both in glia and neurons, to evaluate metabolic compartmentation between glia and neurons. The synthetic CB₁R agonist WIN55212-2 (1 μM) significantly decreased the metabolism of both [2-¹³C]acetate (-11.6±2.0%) and [U-¹³C]glucose (-11.2±3.4%) in the tricarboxylic acid cycle that contributes to the glutamate pool. WIN55212-2 also significantly decreased the metabolism of [U-¹³C]glucose (-11.7±4.0%) but not that of [2-¹³C]acetate contributing to the pool of GABA. These effects of WIN55212-2 were prevented by the CB₁R antagonist AM251 (500 nM). These results thus suggest that CB₁Rs might be present also in hippocampal astrocytes besides their well-known neuronal localization. Indeed, confocal microscopy analysis revealed the presence of specific CB₁R immunoreactivity in astrocytes and pericytes throughout the hippocampus. In conclusion, CB₁Rs are able to control hippocampal intermediary metabolism in both neuronal and glial compartments, which suggests new alternative mechanisms by which CB₁Rs control cell physiology and afford neuroprotection.</p>}},
author = {{Duarte, João M N and Ferreira, Samira G and Carvalho, Rui A. and Cunha, Rodrigo A and Köfalvi, Attila}},
issn = {{0197-0186}},
keywords = {{Animals; Astrocytes; Benzoxazines; Glucose; Glutamic Acid; Hippocampus; Magnetic Resonance Spectroscopy; Male; Morpholines; Naphthalenes; Neurons; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Receptors, Drug; gamma-Aminobutyric Acid; Journal Article; Research Support, Non-U.S. Gov't}},
language = {{eng}},
number = {{1}},
pages = {{1--8}},
publisher = {{Elsevier}},
series = {{Neurochemistry International}},
title = {{CB₁ receptor activation inhibits neuronal and astrocytic intermediary metabolism in the rat hippocampus}},
url = {{http://dx.doi.org/10.1016/j.neuint.2011.10.019}},
doi = {{10.1016/j.neuint.2011.10.019}},
volume = {{60}},
year = {{2012}},
}