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ludc web

Joao Duarte

Principal investigator

ludc web

CB₁ receptor activation inhibits neuronal and astrocytic intermediary metabolism in the rat hippocampus

Author

  • João M N Duarte
  • Samira G Ferreira
  • Rui A. Carvalho
  • Rodrigo A Cunha
  • Attila Köfalvi

Summary, in English

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.

Publishing year

2012-01

Language

English

Pages

1-8

Publication/Series

Neurochemistry International

Volume

60

Issue

1

Document type

Journal article

Publisher

Elsevier

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

Status

Published

ISBN/ISSN/Other

  • ISSN: 0197-0186