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Expertise: endocannabinoïdes, stress, exercice physique

130 publication(s) depuis Janvier 1985:

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25/11/2015 | Hippocampus   IF 4.1
Running per se stimulates the dendritic arbor of newborn dentate granule cells in mouse hippocampus in a duration-dependent manner.
Dostes S, Dubreucq S, Ladeveze E, Marsicano G, Abrous DN, Chaouloff F, Koehl M

Laboratory rodents provided chronic unlimited access to running wheels display increased neurogenesis in the hippocampal dentate gyrus. In addition, recent studies indicate that such an access to wheels stimulates dendritic arborization in newly formed neurons. However, (i) the presence of the running wheel in the housing environment might also bear intrinsic influences on the number and shape of new neurons and (ii) the dendritic arborization of new neurons might be insensitive to moderate daily running activity (i.e. several hours). In keeping with these uncertainties, we have examined neurogenesis and dendritic arborization in newly formed granular cells in adult C57Bl/6N male mice housed for 3 weeks under standard conditions, with a locked wheel, with a running wheel set free 3 h/day, or with a running wheel set permanently free. The results indicate that the presence of a blocked wheel in the home cage increased cell proliferation, but not the number of new neurons while running increased in a duration-dependent manner the number of newborn neurons, as assessed by DCX labeling. Morphological analyses of the dendritic tree of newborn neurons, as identified by BrdU-DCX co-staining, revealed that although the presence of the wheel stimulated their dendritic architecture, the amplitude of this effect was lower than that elicited by running activity, and was found to be running duration-dependent. This article is protected by copyright. All rights reserved.

This study examined the respective influences of cannabinoid type-1 (CB1 ) receptors expressed either in forebrain GABAergic neurons, in cortical glutamatergic neurons or in astrocytes on the turnover rates of the endocannabinoids N-arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), and the non-cannabinoid N-acylethanolamides, palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), in mouse forebrain regions. To this end, conditional mutant mice lacking CB1 receptors from either of these cell types were pretreated systemically with JZL195, a dual inhibitor of fatty acid amide hydrolase, the enzyme degrading AEA, PEA and OEA, and of monoacylglycerol lipase, the main 2-AG-degrading enzyme. The analyses of frontocortical, hippocampal and striatal AEA, 2-AG, PEA and OEA concentrations revealed that their respective baseline concentrations were not influenced by the mouse genotype. On the other hand, the accumulation of frontocortical and/or hippocampal 2-AG levels in JZL195-pretreated mice was dependent on the mouse genotype. Thus, JZL195-induced 2-AG accumulation rates were diminished in the frontal cortex of mice lacking CB1 receptors in glutamatergic neurons whilst their respective values were increased in the frontal cortex and hippocampus of mice lacking these receptors in astrocytes. These genotypic differences occurred with parallel and proportionate changes in the fractional rate constants for degradation of 2-AG, thus providing a mechanism whereby the baseline levels of 2-AG remained constant between genotypes. Besides suggesting a cell-type-specific control of frontocortical and/or hippocampal 2-AG synthesis and degradation rates by CB1 receptors, this study highlights the interest of assessing endocannabinoid turnover rates when questioning the status of the endocannabinoid system. This article is protected by copyright. All rights reserved.

2015 | curr protoc neurosci
To stress or not to stress: a question of models.
Gray JM, Chaouloff F, Hill MN

Stress research is a rapidly evolving field that encompasses numerous disciplines ranging from neuroscience to metabolism. With many new researchers migrating into the field, navigating the hows and whys of specific research questions can sometimes be enigmatic given the availability of so many models in the stress field. Additionally, as with every field, there are many seemingly minor experimental details that can have dramatic influences on data interpretation, although many of these are unknown to those not familiar with the field. The aim of this overview is to provide some suggestions and points to guide researchers moving into the stress field and highlight relevant methodological points that they should consider when choosing a model for stress and deciding how to structure a study. We briefly provide a primer on the basics of endpoint measurements in the stress field, factors to consider when choosing a model for acute stress, the difference between repeated and chronic stress, and importantly, influencing variables that modulate endpoints of analysis in stress work. (c) 2015 by John Wiley & Sons, Inc.

26/12/2014 | Behav Brain Res   IF 3
Duration- and environment-dependent effects of repeated voluntary exercise on anxiety and cued fear in mice.
Dubreucq S, Marsicano G, Chaouloff F

Several studies have indicated that animal models of exercise, such as voluntary wheel running, might be endowed with anxiolytic properties. Using the light/dark test of unconditioned anxiety, we have reported that one confounding factor in the estimation of wheel running impacts on anxiety might be the housing condition of the sedentary controls. The present mouse study analyzed whether the aforementioned observation in the light/dark test (i) could be repeated in the elevated plus-maze and social interaction tests of unconditioned anxiety, (ii) extended to conditioned anxiety, as assessed during cued fear recall tests, and (iii) required unlimited daily access to the running wheel. Housing with a locked wheel or with a free wheel that allowed limited or unlimited running activity triggered anxiolysis in the light/dark test, but not in the elevated plus-maze test, compared to standard housing. In the social interaction test, the duration, but not the number, of social contacts was increased in mice provided unlimited (but not limited) access to a wheel, compared to standard housing or housing with a locked wheel. Lastly, freezing responses to a cue during fear recall tests indicated that the reduction in freezing observed in mice provided limited or unlimited access to the wheels was fully accounted for by housing with a wheel. Besides confirming that the housing condition of the sedentary controls might bias the estimation of the effects of wheel running on anxiety, this study further shows that this estimation is dependent on the test used to assess anxiety.

07/2014 | Mol Metab   IF 5.4
Cannabinoid control of brain bioenergetics: Exploring the subcellular localization of the CB1 receptor.
Hebert-Chatelain E, Reguero L, Puente N, Lutz B, Chaouloff F, Rossignol R, Piazza PV, Benard G, Grandes P, Marsicano G

Brain mitochondrial activity is centrally involved in the central control of energy balance. When studying mitochondrial functions in the brain, however, discrepant results might be obtained, depending on the experimental approaches. For instance, immunostaining experiments and biochemical isolation of organelles expose investigators to risks of false positive and/or false negative results. As an example, the functional presence of cannabinoid type 1 (CB1) receptors on brain mitochondrial membranes (mtCB1) was recently reported and rapidly challenged, claiming that the original observation was likely due to artifact results. Here, we addressed this issue by directly comparing the procedures used in the two studies. Our results show that the use of appropriate controls and quantifications allows detecting mtCB1 receptor with CB1 receptor antibodies, and that, if mitochondrial fractions are enriched and purified, CB1 receptor agonists reliably decrease respiration in brain mitochondria. These data further underline the importance of adapted experimental procedures to study brain mitochondrial functions.

07/2014 | Mol Metab   IF 5.4
Studying mitochondrial CB1 receptors: Yes we can.
Hebert-Chatelain E, Reguero L, Puente N, Lutz B, Chaouloff F, Rossignol R, Piazza PV, Benard G, Grandes P, Marsicano G


11/12/2013 | J Neurosci   IF 5.9
Stress switches cannabinoid type-1 (CB1) receptor-dependent plasticity from LTD to LTP in the bed nucleus of the stria terminalis.
Glangetas C, Girard D, Groc L, Marsicano G, Chaouloff F, Georges F

The bed nucleus of the stria terminalis (BNST) exerts a coordinated modulation of the psychoneuroendocrine responses to stress. However, how acute stress impacts on BNST in vivo plasticity is a crucial question that still remains unanswered. Here, neurons from the anterior portion of the BNST (aBNST) were recorded in vivo during and after stimulation of their medial prefrontal cortical (mPFC) afferents. In C57BL/6N mice, a 1 h restraint stress induced a switch from long-term depression (LTD) to long-term potentiation (LTP) in the aBNST after a 10 Hz mPFC stimulation. This switch was independent from glucocorticoid receptor stimulation. Because the endocannabinoid system regulates aBNST activity, we next examined the role of cannabinoid type-1 receptors (CB1-Rs) in these changes. Mutant mice lacking CB1-Rs (CB1(-/-) mice) displayed a marked deficit in the ability to develop plasticity under control and stress conditions, compared with their wild-type littermates (CB1(+/+) mice). This difference was not accounted for by genetic differences in stress sensitivity, as revealed by Fos immunohistochemistry analyses. Local blockade of CB1-Rs in the aBNST and the use of mutant mice bearing a selective deletion of CB1-Rs in cortical glutamatergic neurons indicated that stress-elicited LTP involved CB1-Rs located on aBNST excitatory terminals. These results show that acute stress reverts LTD into LTP in the aBNST and that the endocannabinoid system plays a key role therein.

10/2013 | Cell Tissue Res   IF 2.9
Social stress models in depression research: what do they tell us?
Chaouloff F

Interest has recently surged in the use of social stress models, especially social defeat. Such interest lies both in the recognition that stressors of social origin play a major role in human psychopathologies and in the acknowledgement that natural and hence ethologically-based stress models have important translational value. The use of the most recent technology has allowed the recognition of the mechanisms through which social defeat might have enduring psychoneuroendocrine effects, especially social avoidance and anhedonia, two behaviours relevant to human depression. In view of the sensitivity of these behavioural outcomes to repeated antidepressant treatments, the social defeat model has been proposed as a possible animal model of depression. The present survey is aimed at examining the limits of such an interpretation and focuses on methodological aspects and on the relevance of social defeat to the study of anxiety-related pathologies.

01/05/2013 | Biol Psychiatry   IF 8.9
Ventral tegmental area cannabinoid type-1 receptors control voluntary exercise performance.
Dubreucq S, Durand A, Matias I, Benard G, Richard E, Soria-Gomez E, Glangetas C, Groc L, Wadleigh A, Massa F, Bartsch D, Marsicano G, Georges F, Chaouloff F

BACKGROUND: We have shown that the endogenous stimulation of cannabinoid type-1 (CB(1)) receptors is a prerequisite for voluntary running in mice, but the precise mechanisms through which the endocannabinoid system exerts a tonic control on running performance remain unknown. METHODS: We analyzed the respective impacts of constitutive/conditional CB(1) receptor mutations and of CB(1) receptor blockade on wheel-running performance. We then assessed the consequences of ventral tegmental area (VTA) CB(1) receptor blockade on the wheel-running performances of wildtype (gamma-aminobutyric acid [GABA]-CB(1)(+)/(+)) and mutant (GABA-CB(1)(-)/(-)) mice for CB(1) receptors in brain GABA neurons. Using in vivo electrophysiology, the consequences of wheel running on VTA dopamine (DA) neuronal activity were examined in GABA-CB(1)(+)/(+) and GABA-CB(1)(-)/(-) mice. RESULTS: Conditional deletion of CB(1) receptors from brain GABA neurons, but not from several other neuronal populations or from astrocytes, decreased wheel-running performance in mice. The inhibitory consequences of either the systemic or the intra-VTA administration of CB1 receptor antagonists on running behavior were abolished in GABA-CB(1)(-)/(-) mice. The absence of CB1 receptors from GABAergic neurons led to a depression of VTA DA neuronal activity after acute/repeated wheel running. CONCLUSIONS: This study provides evidence that CB(1) receptors on VTA GABAergic terminals exert a permissive control on rodent voluntary running performance. Furthermore, it is shown that CB(1) receptors located on GABAergic neurons impede negative consequences of voluntary exercise on VTA DA neuronal activity. These results position the endocannabinoid control of inhibitory transmission as a prerequisite for wheel-running performance in mice.

04/2013 | Mol Psychiatry   IF 15
Regulation of AMPA receptor surface trafficking and synaptic plasticity by a cognitive enhancer and antidepressant molecule.
Zhang H, Etherington LA, Hafner AS, Belelli D, Coussen F, Delagrange P, Chaouloff F, Spedding M, Lambert JJ, Choquet D, Groc L

The plasticity of excitatory synapses is an essential brain process involved in cognitive functions, and dysfunctions of such adaptations have been linked to psychiatric disorders such as depression. Although the intracellular cascades that are altered in models of depression and stress-related disorders have been under considerable scrutiny, the molecular interplay between antidepressants and glutamatergic signaling remains elusive. Using a combination of electrophysiological and single nanoparticle tracking approaches, we here report that the cognitive enhancer and antidepressant tianeptine (S 1574, [3-chloro-6-methyl-5,5-dioxo-6,11-dihydro-(c,f)-dibenzo-(1,2-thiazepine)-11-yl) amino]-7 heptanoic acid, sodium salt) favors synaptic plasticity in hippocampal neurons both under basal conditions and after acute stress. Strikingly, tianeptine rapidly reduces the surface diffusion of AMPA receptor (AMPAR) through a Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-dependent mechanism that enhances the binding of AMPAR auxiliary subunit stargazin with PSD-95. This prevents corticosterone-induced AMPAR surface dispersal and restores long-term potentiation of acutely stressed mice. Collectively, these data provide the first evidence that a therapeutically used drug targets the surface diffusion of AMPAR through a CaMKII-stargazin-PSD-95 pathway, to promote long-term synaptic plasticity.