期刊
NEUROCHEMISTRY INTERNATIONAL
卷 60, 期 1, 页码 1-8出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2011.10.019
关键词
CB1 cannabinoid receptor; Intermediary metabolism; Hippocampus; Astrocyte; Neuron; Nuclear magnetic resonance
资金
- Portuguese Government [PTDC/SAU-OSM/105663/2008, PDTC/EBB-EBI/115810/2009, PTDC/SAU-NEU/108668/2008]
- Fundacao Oriente
- FCT [SFRH/BD/17795/2004, SFRH/BD/33467/2008]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/17795/2004, PTDC/SAU-NEU/108668/2008, PTDC/SAU-OSM/105663/2008, SFRH/BD/33467/2008] Funding Source: FCT
Cannabinoid CB1 receptor (CB1R) activation decreases synaptic GABAergic and glutamatergic transmission and it also controls peripheral metabolism. Here we aimed at testing with C-13 NMR isotopomer analysis whether CB(1)Rs 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-C-13]acetate, which is oxidized in glial cells, and [U-C-13]glucose, which is metabolized both in glia and neurons, to evaluate metabolic compartmentation between glia and neurons. The synthetic CB1R agonist WIN55212-2 (1 mu M) significantly decreased the metabolism of both [2-C-13]acetate (-11.6+/-2.0%) and [U-C-13]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-C-13]glucose (-11.7+/-4.0%) but not that of [2-C-13]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 CB(1)Rs might be present also in hippocampal astrocytes besides their well-known neuronal localization. Indeed, confocal microscopy analysis revealed the presence of specific all R immunoreactivity in astrocytes and pericytes throughout the hippocampus. In conclusion, CB(1)Rs are able to control hippocampal intermediary metabolism in both neuronal and glial compartments, which suggests new alternative mechanisms by which CB(1)Rs control cell physiology and afford neuroprotection. (C) 2011 Elsevier Ltd. All rights reserved.
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