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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.

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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
ISSN
0197-0186
DOI
10.1016/j.neuint.2011.10.019
language
English
LU publication?
no
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3f0c688b-3dd1-4a2a-9625-e75516f6fc70
date added to LUP
2017-10-19 15:21:33
date last changed
2017-10-24 10:32:29
@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},
  keyword      = {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},
  volume       = {60},
  year         = {2012},
}