Publications by authors named "Luigi Bellocchio"

44 Publications

Hypothalamic bile acid-TGR5 signaling protects from obesity.

Cell Metab 2021 Apr 19. Epub 2021 Apr 19.

University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300 Bordeaux, France.

Bile acids (BAs) improve metabolism and exert anti-obesity effects through the activation of the Takeda G protein-coupled receptor 5 (TGR5) in peripheral tissues. TGR5 is also found in the brain hypothalamus, but whether hypothalamic BA signaling is implicated in body weight control and obesity pathophysiology remains unknown. Here we show that hypothalamic BA content is reduced in diet-induced obese mice. Central administration of BAs or a specific TGR5 agonist in these animals decreases body weight and fat mass by activating the sympathetic nervous system, thereby promoting negative energy balance. Conversely, genetic downregulation of hypothalamic TGR5 expression in the mediobasal hypothalamus favors the development of obesity and worsens established obesity by blunting sympathetic activity. Lastly, hypothalamic TGR5 signaling is required for the anti-obesity action of dietary BA supplementation. Together, these findings identify hypothalamic TGR5 signaling as a key mediator of a top-down neural mechanism that counteracts diet-induced obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmet.2021.04.009DOI Listing
April 2021

Subcellular specificity of cannabinoid effects in striatonigral circuits.

Neuron 2021 05 25;109(9):1513-1526.e11. Epub 2021 Mar 25.

INSERM, U1215 NeuroCentre Magendie, Endocannabinoids and Neuroadaptation, Bordeaux, France; University of Bordeaux, Bordeaux, France.

Recent advances in neuroscience have positioned brain circuits as key units in controlling behavior, implying that their positive or negative modulation necessarily leads to specific behavioral outcomes. However, emerging evidence suggests that the activation or inhibition of specific brain circuits can actually produce multimodal behavioral outcomes. This study shows that activation of a receptor at different subcellular locations in the same neuronal circuit can determine distinct behaviors. Pharmacological activation of type 1 cannabinoid (CB) receptors in the striatonigral circuit elicits both antinociception and catalepsy in mice. The decrease in nociception depends on the activation of plasma membrane-residing CB receptors (pmCB), leading to the inhibition of cytosolic PKA activity and substance P release. By contrast, mitochondrial-associated CB receptors (mtCB) located at the same terminals mediate cannabinoid-induced catalepsy through the decrease in intra-mitochondrial PKA-dependent cellular respiration and synaptic transmission. Thus, subcellular-specific CB receptor signaling within striatonigral circuits determines multimodal control of behavior.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuron.2021.03.007DOI Listing
May 2021

CB1 and GLP-1 Receptors Cross Talk Provides New Therapies for Obesity.

Diabetes 2021 02 3;70(2):415-422. Epub 2020 Nov 3.

University of Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France

Glucagon-like peptide 1 receptor (GLP-1R) agonists effectively improve glycemia and body weight in patients with type 2 diabetes and obesity but have limited weight-lowering efficacy and minimal insulin sensitizing action. In preclinical models, peripherally restricted cannabinoid receptor type 1 (CB1R) inhibitors, which are devoid of the neuropsychiatric adverse effects observed with brain-penetrant CB1R blockers, ameliorate obesity and its multiple metabolic complications. Using mouse models with genetic loss of CB1R or GLP-1R, we demonstrate that these two metabolic receptors modulate food intake and body weight via reciprocal functional interactions. In diet-induced obese mice, the coadministration of a peripheral CB1R inhibitor with long-acting GLP-1R agonists achieves greater reduction in body weight and fat mass than monotherapies by promoting negative energy balance. This cotreatment also results in larger improvements in systemic and hepatic insulin action, systemic dyslipidemia, and reduction of hepatic steatosis. Thus, peripheral CB1R blockade may allow safely potentiating the antiobesity and antidiabetic effects of currently available GLP-1R agonists.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/db20-0162DOI Listing
February 2021

Environmental Issues and Neurological Manifestations Associated with COVID-19 Pandemic: New Aspects of the Disease?

Int J Environ Res Public Health 2020 11 1;17(21). Epub 2020 Nov 1.

Department of Environmental Sciences and Policy, University of Milan, 20068 Milan, Italy.

Coronavirus (SARS-CoV-2) emerged in China in December 2019 and rapidly caused a global health pandemic. Current evidence seems to suggest a possible link with ecosystem disequilibrium and even air pollution. The primary manifestations affect respiratory and circulatory systems, but neurological features are also being reported through case reports and case series. We summarize neurological symptoms and complications associated with COVID-19. We have searched for original articles published in PubMed/Medline, PubMed Central and Google Scholar using the following keywords: "COVID-19", "Coronavirus", "pandemic", "SARS-COV-2", "neurology", "neurological", "complications" and "manifestations". We found around 1000 publications addressing the issue of neurological conditions associated with COVID-19 infection. Amongst those, headache and dizziness are the most common reported symptoms followed by encephalopathy and delirium, while the most frequent complications are cerebrovascular accidents, Guillain-Barré syndrome, acute transverse myelitis, and acute encephalitis. Specific symptoms affecting the peripheral nervous system such as hyposmia and dysgeusia are the most common manifestations recorded in the selected studies. Interestingly, it was noted that these kinds of neurological symptoms might precede the typical features, such as fever and cough, in COVID patients. Neurological symptoms and complications associated with COVID-19 should be considered as a part of the clinical features of this novel global pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph17218049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663018PMC
November 2020

A Novel Cortical Mechanism for Top-Down Control of Water Intake.

Curr Biol 2020 12 8;30(23):4789-4798.e4. Epub 2020 Oct 8.

INSERM, U1215 NeuroCentre Magendie, 146 rue Léo Saignat, 33077 Bordeaux Cedex, France; University of Bordeaux, 146 rue Léo Saignat, 33000 Bordeaux, France. Electronic address:

Water intake is crucial for maintaining body fluid homeostasis and animals' survival [1-4]. In the brain, complex processes trigger thirst and drinking behavior [1-5]. The anterior wall of the third ventricle formed by the subfornical organ (SFO), the median preoptic nucleus, and the organum vasculosum of the lamina terminalis (OVLT) constitute the primary structures sensing thirst signals and modulating water intake [6-10]. These subcortical regions are connected with the neocortex [11]. In particular, insular and anterior cingulate cortices (IC and ACC, respectively) have been shown to receive indirect innervations from the SFO and OVLT in rats [11] and to be involved in the control of water intake [12-15]. Type-1 cannabinoid receptors (CB) modulate consummatory behaviors, such as feeding [16-26]. However, the role of CB receptors in the control of water intake is still a matter of debate [27-31]. Here, we show that endogenous activation of CB in cortical glutamatergic neurons of the ACC promotes water intake. Notably, presynaptic CB receptors of ACC glutamatergic neurons are abundantly located in the basolateral amygdala (BLA), a key area in the regulation of water intake. The selective expression of CB receptors in the ACC-to-BLA-projecting neurons is sufficient to stimulate drinking behavior. Moreover, chemogenetic stimulation of these projecting neurons suppresses drinking behavior, further supporting the role of this neuronal population in the control of water intake. Altogether, these data reveal a novel cortico-amygdalar mechanism involved in the regulation of drinking behavior.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cub.2020.09.011DOI Listing
December 2020

Cannabinoid-induced motor dysfunction autophagy inhibition.

Autophagy 2020 12 20;16(12):2289-2291. Epub 2020 Oct 20.

Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, Instituto Universitario de Investigación Neuroquímica (IUIN) , Madrid, Spain.

The recreational and medical use of cannabis is largely increasing worldwide. Cannabis use, however, can cause adverse side effects, so conducting innovative studies aimed to understand and potentially reduce cannabis-evoked harms is important. Previous research conducted on cultured neural cells had supported that CNR1/CBR (cannabinoid receptor 1), the main molecular target of cannabis, affects macroautophagy/autophagy. However, it was not known whether CNR1 controls autophagy in the brain , and, eventually, what the functional consequences of a potential CNR1-autophagy connection could be. We have now found that Δ-tetrahydrocannabinol (THC), the major intoxicating constituent of cannabis, impairs autophagy in the mouse striatum. Administration of autophagy activators (specifically, the rapalog temsirolimus and the disaccharide trehalose) rescues THC-induced autophagy inhibition and motor dyscoordination. The combination of various genetic strategies supports the idea that CNR1 molecules located on neurons belonging to the direct (striatonigral) pathway are required for the autophagy- and motor-impairing activity of THC. By identifying autophagy as a mechanistic link between THC and motor performance, our findings may open a new conceptual view on how cannabis acts in the brain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15548627.2020.1827560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751656PMC
December 2020

Specific Hippocampal Interneurons Shape Consolidation of Recognition Memory.

Cell Rep 2020 08;32(7):108046

INSERM U1215, NeuroCentre Magendie, Bordeaux 33300, France; University of Bordeaux, Bordeaux 33300, France; Ikerbasque-Basque Foundation for Science, Bilbao 48013, Spain; Department of Neuroscience, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU) Leioa 48940, Spain; Achucarro Basque Center for Neuroscience, Leioa 48940, Spain. Electronic address:

A complex array of inhibitory interneurons tightly controls hippocampal activity, but how such diversity specifically affects memory processes is not well understood. We find that a small subclass of type 1 cannabinoid receptor (CBR)-expressing hippocampal interneurons determines episodic-like memory consolidation by linking dopamine D receptor (DR) signaling to GABAergic transmission. Mice lacking CBRs in D-positive cells (D-CB-KO) display impairment in long-term, but not short-term, novel object recognition memory (NOR). Re-expression of CBRs in hippocampal DR-positive cells rescues this NOR deficit. Learning induces an enhancement of in vivo hippocampal long-term potentiation (LTP), which is absent in mutant mice. CBR-mediated NOR and the associated LTP facilitation involve local control of GABAergic inhibition in a D-dependent manner. This study reveals that hippocampal CBR-/DR-expressing interneurons control NOR memory, identifying a mechanism linking the diversity of hippocampal interneurons to specific behavioral outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2020.108046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443618PMC
August 2020

Inhibition of striatonigral autophagy as a link between cannabinoid intoxication and impairment of motor coordination.

Elife 2020 08 10;9. Epub 2020 Aug 10.

Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto Universitario de Investigación Neuroquímica (IUIN) and Department of Biochemistry and Molecular Biology, Complutense University, Madrid, Spain.

The use of cannabis is rapidly expanding worldwide. Thus, innovative studies aimed to identify, understand and potentially reduce cannabis-evoked harms are warranted. Here, we found that Δ-tetrahydrocannabinol, the psychoactive ingredient of cannabis, disrupts autophagy selectively in the striatum, a brain area that controls motor behavior, both in vitro and in vivo. Boosting autophagy, either pharmacologically (with temsirolimus) or by dietary intervention (with trehalose), rescued the Δ-tetrahydrocannabinol-induced impairment of motor coordination in mice. The combination of conditional knockout mouse models and viral vector-mediated autophagy-modulating strategies in vivo showed that cannabinoid CB receptors located on neurons belonging to the direct (striatonigral) pathway are required for the motor-impairing activity of Δ-tetrahydrocannabinol by inhibiting local autophagy. Taken together, these findings identify inhibition of autophagy as an unprecedented mechanistic link between cannabinoids and motor performance, and suggest that activators of autophagy might be considered as potential therapeutic tools to treat specific cannabinoid-evoked behavioral alterations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.56811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417168PMC
August 2020

The role of the endocannabinoid system in autism spectrum disorders: Evidence from mouse studies.

Prog Mol Biol Transl Sci 2020 23;173:183-208. Epub 2020 May 23.

Department of Rehabilitation Sciences, Faculty of Health & Social Sciences, The Hong Kong Polytechnic University, Hong Kong, China.

A substantive volume of research on autism spectrum disorder (ASD) has emerged in recent years adding to our understanding of the etiopathological process. Preclinical models in mice and rats have been highly instrumental in modeling and dissecting the contributions of a multitude of known genetic and environmental risk factors. However, the translation of preclinical data into suitable drug targets must overcome three critical hurdles: (i) ASD comprises a highly heterogeneous group of conditions that can markedly differ in terms of their clinical presentation and symptoms, (ii) the plethora of genetic and environmental risk factors suggests a complex, non-unitary, etiopathology, and (iii) the lack of consensus over the myriad of preclinical models, with respect to both construct validity and face validity. Against this backdrop, this Chapter traces how the endocannabinoid system (ECS) has emerged as a promising target for intervention with predictive validity. Recent supportive preclinical evidence is summarized, especially studies in mice demonstrating the emergence of ASD-like behaviors following diverse genetic or pharmacological manipulations targeting the ECS. The critical relevance of ECS to the complex pathogenesis of ASD is underscored by its multiple roles in modulating neuronal functions and shaping brain development. Finally, we argue that important lessons have been learned from the novel mouse models of ASD, which not only stimulate game-changing innovative treatments but also foster a consensual framework to integrate the diverse approaches applied in the search of novel treatments for ASD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/bs.pmbts.2020.04.016DOI Listing
June 2021

Glucose metabolism links astroglial mitochondria to cannabinoid effects.

Nature 2020 07 8;583(7817):603-608. Epub 2020 Jul 8.

INSERM, U1215 NeuroCentre Magendie, Bordeaux, France.

Astrocytes take up glucose from the bloodstream to provide energy to the brain, thereby allowing neuronal activity and behavioural responses. By contrast, astrocytes are under neuronal control through specific neurotransmitter receptors. However, whether the activation of astroglial receptors can directly regulate cellular glucose metabolism to eventually modulate behavioural responses is unclear. Here we show that activation of mouse astroglial type-1 cannabinoid receptors associated with mitochondrial membranes (mtCB) hampers the metabolism of glucose and the production of lactate in the brain, resulting in altered neuronal functions and, in turn, impaired behavioural responses in social interaction assays. Specifically, activation of astroglial mtCB receptors reduces the phosphorylation of the mitochondrial complex I subunit NDUFS4, which decreases the stability and activity of complex I. This leads to a reduction in the generation of reactive oxygen species by astrocytes and affects the glycolytic production of lactate through the hypoxia-inducible factor 1 pathway, eventually resulting in neuronal redox stress and impairment of behavioural responses in social interaction assays. Genetic and pharmacological correction of each of these effects abolishes the effect of cannabinoid treatment on the observed behaviour. These findings suggest that mtCB receptor signalling can directly regulate astroglial glucose metabolism to fine-tune neuronal activity and behaviour in mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-020-2470-yDOI Listing
July 2020

Author Correction: Structural basis of astrocytic Ca signals at tripartite synapses.

Nat Commun 2020 05 18;11(1):2541. Epub 2020 May 18.

Interdisciplinary Institute for Neuroscience, University of Bordeaux, Bordeaux, France.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-16453-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235234PMC
May 2020

Structural basis of astrocytic Ca signals at tripartite synapses.

Nat Commun 2020 04 20;11(1):1906. Epub 2020 Apr 20.

University of Bordeaux, Bordeaux, France.

Astrocytic Ca signals can be fast and local, supporting the idea that astrocytes have the ability to regulate single synapses. However, the anatomical basis of such specific signaling remains unclear, owing to difficulties in resolving the spongiform domain of astrocytes where most tripartite synapses are located. Using 3D-STED microscopy in living organotypic brain slices, we imaged the spongiform domain of astrocytes and observed a reticular meshwork of nodes and shafts that often formed loop-like structures. These anatomical features were also observed in acute hippocampal slices and in barrel cortex in vivo. The majority of dendritic spines were contacted by nodes and their sizes were correlated. FRAP experiments and Ca imaging showed that nodes were biochemical compartments and Ca microdomains. Mapping astrocytic Ca signals onto STED images of nodes and dendritic spines showed they were associated with individual synapses. Here, we report on the nanoscale organization of astrocytes, identifying nodes as a functional astrocytic component of tripartite synapses that may enable synapse-specific communication between neurons and astrocytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-15648-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170846PMC
April 2020

Dopamine-Evoked Synaptic Regulation in the Nucleus Accumbens Requires Astrocyte Activity.

Neuron 2020 03 15;105(6):1036-1047.e5. Epub 2020 Jan 15.

Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:

Dopamine is involved in physiological processes like learning and memory, motor control and reward, and pathological conditions such as Parkinson's disease and addiction. In contrast to the extensive studies on neurons, astrocyte involvement in dopaminergic signaling remains largely unknown. Using transgenic mice, optogenetics, and pharmacogenetics, we studied the role of astrocytes on the dopaminergic system. We show that in freely behaving mice, astrocytes in the nucleus accumbens (NAc), a key reward center in the brain, respond with Ca elevations to synaptically released dopamine, a phenomenon enhanced by amphetamine. In brain slices, synaptically released dopamine increases astrocyte Ca, stimulates ATP/adenosine release, and depresses excitatory synaptic transmission through activation of presynaptic A receptors. Amphetamine depresses neurotransmission through stimulation of astrocytes and the consequent A receptor activation. Furthermore, astrocytes modulate the acute behavioral psychomotor effects of amphetamine. Therefore, astrocytes mediate the dopamine- and amphetamine-induced synaptic regulation, revealing a novel cellular pathway in the brain reward system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuron.2019.12.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322729PMC
March 2020

Alpha technology: A powerful tool to detect mouse brain intracellular signaling events.

J Neurosci Methods 2020 02 9;332:108543. Epub 2019 Dec 9.

INSERM U1215, NeuroCentre Magendie, 33077 Bordeaux, France; University of Bordeaux, 33077 Bordeaux, France. Electronic address:

Background: Phosphorylation by protein kinases is a fundamental molecular process involved in the regulation of signaling activities in living organisms. Understanding this complex network of phosphorylation, especially phosphoproteins, is a necessary step for grasping the basis of cellular pathophysiology. Studying brain intracellular signaling is a particularly complex task due to the heterogeneous complex nature of the brain tissue, which consists of many embedded structures.

New Method: Overcoming this degree of complexity requires a technology with a high throughput and economical in the amount of biological material used, so that a large number of signaling pathways may be analyzed in a large number of samples. We have turned to Alpha (Amplified Luminescent Proximity Homogeneous Assay) technology.

Comparison With Existing Method: Western blot is certainly the most commonly used method to measure the phosphorylation state of proteins. Even though Western blot is an accurate and reliable method for analyzing modifications of proteins, it is a time-consuming and large amounts of samples are required. Those two parameters are critical when the goal of the research is to comprehend multi-signaling proteic events so as to analyze several targets from small brain areas.

Result: Here we demonstrate that Alpha technology is particularly suitable for studying brain signaling pathways by allowing rapid, sensitive, reproducible and semi-quantitative detection of phosphoproteins from individual mouse brain tissue homogenates and from cell fractionation and synaptosomal preparations of mouse hippocampus.

Conclusion: Alpha technology represents a major experimental step forward in unraveling the brain phosphoprotein-related molecular mechanisms involved in brain-related disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jneumeth.2019.108543DOI Listing
February 2020

CB1 Receptors in the Anterior Piriform Cortex Control Odor Preference Memory.

Curr Biol 2019 08 18;29(15):2455-2464.e5. Epub 2019 Jul 18.

INSERM, U1215 NeuroCentre Magendie, 146 rue Léo Saignat, 33077 Bordeaux Cedex, France; University of Bordeaux, 146 rue Léo Saignat, 33000 Bordeaux, France. Electronic address:

The retrieval of odor-related memories shapes animal behavior. The anterior piriform cortex (aPC) is the largest part of the olfactory cortex, and it plays important roles in olfactory processing and memory. However, it is still unclear whether specific cellular mechanisms in the aPC control olfactory memory, depending on the appetitive or aversive nature of the stimuli involved. Cannabinoid-type 1 (CB1) receptors are present in the aPC (aPC-CB1), but their potential impact on olfactory memory was never explored. Here, we used a combination of behavioral, genetic, anatomical, and electrophysiological approaches to characterize the functions of aPC-CB1 receptors in the regulation of appetitive and aversive olfactory memory. Pharmacological blockade or genetic deletion of aPC-CB1 receptors specifically impaired the retrieval of conditioned odor preference (COP). Interestingly, expression of conditioned odor aversion (COA) was unaffected by local CB1 receptor blockade, indicating that the role of aPC endocannabinoid signaling is selective for retrieval of appetitive memory. Anatomical investigations revealed that CB1 receptors are highly expressed on aPC GABAergic interneurons, and ex vivo electrophysiological recordings showed that their pharmacological activation reduces miniature inhibitory post-synaptic currents (mIPSCs) onto aPC semilunar (SL), but not pyramidal principal neurons. COP retrieval, but not COA, was associated with a specific CB1-receptor-dependent decrease of mIPSCs in SL cells. Altogether, these data indicate that aPC-CB1 receptor-dependent mechanisms physiologically control the retrieval of olfactory memory, depending on odor valence and engaging modulation of local inhibitory transmission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cub.2019.06.041DOI Listing
August 2019

Astroglial monoacylglycerol lipase controls mutant huntingtin-induced damage of striatal neurons.

Neuropharmacology 2019 05 23;150:134-144. Epub 2019 Mar 23.

Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto Universitario de Investigación Neuroquímica (IUIN), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) and Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University, 28040 Madrid, Spain. Electronic address:

Cannabinoids exert neuroprotection in a wide array of preclinical models. A number of these studies has focused on cannabinoid CB receptors in striatal medium spiny neurons (MSNs) and the most characteristic MSN-degenerative disease, Huntington's disease (HD). Accruing evidence supports that astrocytes contribute to drive HD progression, and that they express CB receptors, degrade endocannabinoids, and modulate endocannabinergic transmission. However, the possible role of the astroglial endocannabinoid system in controlling MSN integrity remains unknown. Here, we show that JZL-184, a selective inhibitor of monoacylglycerol lipase (MGL), the key enzyme that deactivates the endocannabinoid 2-arachidonoylglycerol, prevented the mutant huntingtin-induced up-regulation of the pro-inflammatory cytokine tumor necrosis factor-α in primary mouse striatal astrocytes via CB receptors. To study the role of astroglial MGL in vivo, we injected stereotactically into the mouse dorsal striatum viral vectors that encode mutant or normal huntingtin under the control of the glial fibrillary acidic protein promoter. We observed that, in wild-type mice, pharmacological blockade of MGL with JZL-184 (8 mg/kg/day, i.p.) conferred neuroprotection against mutant huntingtin-induced striatal damage, as evidenced by the prevention of MSN loss, astrogliosis, and motor coordination impairment. We next found that conditional mutant mice bearing a genetic deletion of MGL selectively in astroglial cells (MGL mice) were resistant to mutant huntingtin-induced MSN loss, astrogliosis, and motor coordination impairment. Taken together, these data support that astroglial MGL controls the availability of a 2-arachidonoylglycerol pool that ensues protection of MSNs in the mouse striatum in vivo, thus providing a potential druggable target for reducing striatal neurodegeneration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuropharm.2019.03.027DOI Listing
May 2019

Functional identity of hypothalamic melanocortin neurons depends on Tbx3.

Nat Metab 2019 02 28;1(2):222-235. Epub 2019 Jan 28.

Naomi Berrie Diabetes Center, Columbia Stem Cell Initiative, Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.

Heterogeneous populations of hypothalamic neurons orchestrate energy balance via the release of specific signatures of neuropeptides. However, how specific intracellular machinery controls peptidergic identities and function of individual hypothalamic neurons remains largely unknown. The transcription factor T-box 3 (Tbx3) is expressed in hypothalamic neurons sensing and governing energy status, whereas human TBX3 haploinsufficiency has been linked with obesity. Here, we demonstrate that loss of Tbx3 function in hypothalamic neurons causes weight gain and other metabolic disturbances by disrupting both the peptidergic identity and plasticity of Pomc/Cart and Agrp/Npy neurons. These alterations are observed after loss of Tbx3 in both immature hypothalamic neurons and terminally differentiated mouse neurons. We further establish the importance of Tbx3 for body weight regulation in Drosophila melanogaster and show that TBX3 is implicated in the differentiation of human embryonic stem cells into hypothalamic Pomc neurons. Our data indicate that Tbx3 directs the terminal specification of neurons as functional components of the melanocortin system and is required for maintaining their peptidergic identity. In summary, we report the discovery of a key mechanistic process underlying the functional heterogeneity of hypothalamic neurons governing body weight and systemic metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s42255-018-0028-1DOI Listing
February 2019

Astroglial CB Receptors Determine Synaptic D-Serine Availability to Enable Recognition Memory.

Neuron 2018 06 17;98(5):935-944.e5. Epub 2018 May 17.

INSERM U1215, NeuroCentre Magendie, 33077 Bordeaux, France; University of Bordeaux, 33077 Bordeaux, France. Electronic address:

Bidirectional communication between neurons and astrocytes shapes synaptic plasticity and behavior. D-serine is a necessary co-agonist of synaptic N-methyl-D-aspartate receptors (NMDARs), but the physiological factors regulating its impact on memory processes are scantly known. We show that astroglial CB receptors are key determinants of object recognition memory by determining the availability of D-serine at hippocampal synapses. Mutant mice lacking CB receptors from astroglial cells (GFAP-CB-KO) displayed impaired object recognition memory and decreased in vivo and in vitro long-term potentiation (LTP) at CA3-CA1 hippocampal synapses. Activation of CB receptors increased intracellular astroglial Ca levels and extracellular levels of D-serine in hippocampal slices. Accordingly, GFAP-CB-KO displayed lower occupancy of the co-agonist binding site of synaptic hippocampal NMDARs. Finally, elevation of D-serine levels fully rescued LTP and memory impairments of GFAP-CB-KO mice. These data reveal a novel mechanism of in vivo astroglial control of memory and synaptic plasticity via the D-serine-dependent control of NMDARs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuron.2018.04.034DOI Listing
June 2018

Localization of the cannabinoid type-1 receptor in subcellular astrocyte compartments of mutant mouse hippocampus.

Glia 2018 07 26;66(7):1417-1431. Epub 2018 Feb 26.

Department of Neurosciences, University of the Basque Country UPV/EHU, Leioa, E-48940, Spain.

Astroglial type-1 cannabinoid (CB ) receptors are involved in synaptic transmission, plasticity and behavior by interfering with the so-called tripartite synapse formed by pre- and post-synaptic neuronal elements and surrounding astrocyte processes. However, little is known concerning the subcellular distribution of astroglial CB receptors. In particular, brain CB receptors are mostly localized at cells' plasmalemma, but recent evidence indicates their functional presence in mitochondrial membranes. Whether CB receptors are present in astroglial mitochondria has remained unknown. To investigate this issue, we included conditional knock-out mice lacking astroglial CB receptor expression specifically in glial fibrillary acidic protein (GFAP)-containing astrocytes (GFAP-CB -KO mice) and also generated genetic rescue mice to re-express CB receptors exclusively in astrocytes (GFAP-CB -RS). To better identify astroglial structures by immunoelectron microscopy, global CB knock-out (CB -KO) mice and wild-type (CB -WT) littermates were intra-hippocampally injected with an adeno-associated virus expressing humanized renilla green fluorescent protein (hrGFP) under the control of human GFAP promoter to generate GFAPhrGFP-CB -KO and -WT mice, respectively. Furthermore, double immunogold (for CB ) and immunoperoxidase (for GFAP or hrGFP) revealed that CB receptors are present in astroglial mitochondria from different hippocampal regions of CB -WT, GFAP-CB -RS and GFAPhrGFP-CB -WT mice. Only non-specific gold particles were detected in mouse hippocampi lacking CB receptors. Altogether, we demonstrated the existence of a precise molecular architecture of the CB receptor in astrocytes that will have to be taken into account in evaluating the functional activity of cannabinergic signaling at the tripartite synapse.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/glia.23314DOI Listing
July 2018

Endocannabinoid Actions on Cortical Terminals Orchestrate Local Modulation of Dopamine Release in the Nucleus Accumbens.

Neuron 2017 Dec;96(5):1112-1126.e5

Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, US National Institutes of Health, Rockville, MD, USA. Electronic address:

Dopamine (DA) transmission mediates numerous aspects of behavior. Although DA release is strongly linked to firing of DA neurons, recent developments indicate the importance of presynaptic modulation at striatal dopaminergic terminals. The endocannabinoid (eCB) system regulates DA release and is a canonical gatekeeper of goal-directed behavior. Here we report that extracellular DA increases induced by selective optogenetic activation of cholinergic neurons in the nucleus accumbens (NAc) are inhibited by CB1 agonists and eCBs. This modulation requires CB1 receptors on cortical glutamatergic afferents. Dopamine increases driven by optogenetic activation of prefrontal cortex (PFC) terminals in the NAc are similarly modulated by activation of these CB1 receptors. We further demonstrate that this same population of CB1 receptors modulates optical self-stimulation sustained by activation of PFC afferents in the NAc. These results establish local eCB actions on PFC terminals within the NAc that inhibit mesolimbic DA release and constrain reward-driven behavior.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuron.2017.11.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728656PMC
December 2017

Pathway-Specific Control of Striatal Neuron Vulnerability by Corticostriatal Cannabinoid CB1 Receptors.

Cereb Cortex 2018 01;28(1):307-322

Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto Universitario de Investigación Neuroquímica (IUIN) and Department of Biochemistry and Molecular Biology I, Complutense University, 28040 Madrid, Spain.

The vast majority of neurons within the striatum are GABAergic medium spiny neurons (MSNs), which receive glutamatergic input from the cortex and thalamus, and form two major efferent pathways: the direct pathway, expressing dopamine D1 receptor (D1R-MSNs), and the indirect pathway, expressing dopamine D2 receptor (D2R-MSNs). While molecular mechanisms of MSN degeneration have been identified in animal models of striatal damage, the molecular factors that dictate a selective vulnerability of D1R-MSNs or D2R-MSNs remain unknown. Here, we combined genetic, chemogenetic, and pharmacological strategies with behavioral and neurochemical analyses, and show that the pool of cannabinoid CB1 receptor (CB1R) located on corticostriatal terminals efficiently safeguards D1R-MSNs, but not D2R-MSNs, from different insults. This cell-specific response relies on the regulation of glutamatergic signaling, and is independent from the CB1R-dependent control of astroglial activity in the striatum. These findings define cortical CB1R as a pivotal synaptic player in dictating a differential vulnerability of D1R-MSNs versus D2R-MSNs, and increase our understanding of the role of coordinated cannabinergic-glutamatergic signaling in establishing corticostriatal circuits and its dysregulation in neurodegenerative diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cercor/bhx285DOI Listing
January 2018

A cannabinoid link between mitochondria and memory.

Nature 2016 11 9;539(7630):555-559. Epub 2016 Nov 9.

INSERM U1215, NeuroCentre Magendie, Bordeaux 33077, France.

Cellular activity in the brain depends on the high energetic support provided by mitochondria, the cell organelles which use energy sources to generate ATP. Acute cannabinoid intoxication induces amnesia in humans and animals, and the activation of type-1 cannabinoid receptors present at brain mitochondria membranes (mtCB) can directly alter mitochondrial energetic activity. Although the pathological impact of chronic mitochondrial dysfunctions in the brain is well established, the involvement of acute modulation of mitochondrial activity in high brain functions, including learning and memory, is unknown. Here, we show that acute cannabinoid-induced memory impairment in mice requires activation of hippocampal mtCB receptors. Genetic exclusion of CB receptors from hippocampal mitochondria prevents cannabinoid-induced reduction of mitochondrial mobility, synaptic transmission and memory formation. mtCB receptors signal through intra-mitochondrial Gα protein activation and consequent inhibition of soluble-adenylyl cyclase (sAC). The resulting inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system eventually leads to decreased cellular respiration. Hippocampal inhibition of sAC activity or manipulation of intra-mitochondrial PKA signalling or phosphorylation of the Complex I subunit NDUFS2 inhibit bioenergetic and amnesic effects of cannabinoids. Thus, the G protein-coupled mtCB receptors regulate memory processes via modulation of mitochondrial energy metabolism. By directly linking mitochondrial activity to memory formation, these data reveal that bioenergetic processes are primary acute regulators of cognitive functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nature20127DOI Listing
November 2016

Sustained Gq-Protein Signaling Disrupts Striatal Circuits via JNK.

J Neurosci 2016 10;36(41):10611-10624

Department of Biochemistry and Molecular Biology I, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), and Instituto Universitario de Investigación Neuroquímica (IUIN), Complutense University, 28040 Madrid, Spain, and

The dorsal striatum is a major input structure of the basal ganglia and plays a key role in the control of vital processes such as motor behavior, cognition, and motivation. The functionality of striatal neurons is tightly controlled by various metabotropic receptors. Whereas the G/G-protein-dependent tuning of striatal neurons is fairly well known, the precise impact and underlying mechanism of G-protein-dependent signals remain poorly understood. Here, using different experimental approaches, especially designer receptor exclusively activated by designer drug (DREADD) chemogenetic technology, we found that sustained activation of G-protein signaling impairs the functionality of striatal neurons and we unveil the precise molecular mechanism underlying this process: a phospholipase C/Ca/proline-rich tyrosine kinase 2/cJun N-terminal kinase pathway. Moreover, engagement of this intracellular signaling route was functionally active in the mouse dorsal striatum in vivo, as proven by the disruption of neuronal integrity and behavioral tasks. To analyze this effect anatomically, we manipulated G-protein-dependent signaling selectively in neurons belonging to the direct or indirect striatal pathway. Acute G-protein activation in direct-pathway or indirect-pathway neurons produced an enhancement or a decrease, respectively, of activity-dependent parameters. In contrast, sustained G-protein activation impaired the functionality of direct-pathway and indirect-pathway neurons and disrupted the behavioral performance and electroencephalography-related activity tasks controlled by either anatomical framework. Collectively, these findings define the molecular mechanism and functional relevance of G-protein-driven signals in striatal circuits under normal and overactivated states.

Significance Statement: The dorsal striatum is a major input structure of the basal ganglia and plays a key role in the control of vital processes such as motor behavior, cognition, and motivation. Whereas the G/G-protein-dependent tuning of striatal neurons is fairly well known, the precise impact and underlying mechanism of G-protein-dependent signals remain unclear. Here, we show that striatal circuits can be "turned on" by acute G-protein signaling or "turned off" by sustained G-protein signaling. Specifically, sustained G-protein signaling inactivates striatal neurons by an intracellular pathway that relies on cJun N-terminal kinase. Overall, this study sheds new light onto the molecular mechanism and functional relevance of G-protein-driven signals in striatal circuits under normal and overactivated states.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1523/JNEUROSCI.1192-16.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601931PMC
October 2016

Peripheral and central CB1 cannabinoid receptors control stress-induced impairment of memory consolidation.

Proc Natl Acad Sci U S A 2016 08 15;113(35):9904-9. Epub 2016 Aug 15.

Laboratory of Neuropharmacology-NeuroPhar, Department of Experimental and Health Sciences, University Pompeu Fabra, 08003 Barcelona, Spain;

Stressful events can generate emotional memories linked to the traumatic incident, but they also can impair the formation of nonemotional memories. Although the impact of stress on emotional memories is well studied, much less is known about the influence of the emotional state on the formation of nonemotional memories. We used the novel object-recognition task as a model of nonemotional memory in mice to investigate the underlying mechanism of the deleterious effect of stress on memory consolidation. Systemic, hippocampal, and peripheral blockade of cannabinoid type-1 (CB1) receptors abolished the stress-induced memory impairment. Genetic deletion and rescue of CB1 receptors in specific cell types revealed that the CB1 receptor population specifically in dopamine β-hydroxylase (DBH)-expressing cells is both necessary and sufficient for stress-induced impairment of memory consolidation, but CB1 receptors present in other neuronal populations are not involved. Strikingly, pharmacological manipulations in mice expressing CB1 receptors exclusively in DBH(+) cells revealed that both hippocampal and peripheral receptors mediate the impact of stress on memory consolidation. Thus, CB1 receptors on adrenergic and noradrenergic cells provide previously unrecognized cross-talk between central and peripheral mechanisms in the stress-dependent regulation of nonemotional memory consolidation, suggesting new potential avenues for the treatment of cognitive aspects on stress-related disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1525066113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024630PMC
August 2016

Cannabinoid receptor type-1: breaking the dogmas.

F1000Res 2016 24;5. Epub 2016 May 24.

Endocannabinoids and Neuroadaptation, INSERM U1215 NeuroCentre Magendie, Bordeaux, 33077, France; University of Bordeaux, Bordeaux, France.

The endocannabinoid system (ECS) is abundantly expressed in the brain. This system regulates a plethora of physiological functions and is composed of cannabinoid receptors, their endogenous ligands (endocannabinoids), and the enzymes involved in the metabolism of endocannabinoids. In this review, we highlight the new advances in cannabinoid signaling, focusing on a key component of the ECS, the type-1 cannabinoid receptor (CB 1). In recent years, the development of new imaging and molecular tools has demonstrated that this receptor can be distributed in many cell types (e.g., neuronal or glial cells) and intracellular compartments (e.g., mitochondria). Interestingly, cellular and molecular effects are differentially mediated by CB 1 receptors according to their specific localization (e.g., glutamatergic or GABAergic neurons). Moreover, this receptor is expressed in the periphery, where it can modulate periphery-brain connections. Finally, the better understanding of the CB 1 receptor structure led researchers to propose interesting and new allosteric modulators. Thus, the advances and the new directions of the CB 1 receptor field will provide new insights and better approaches to profit from its interesting therapeutic profile.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12688/f1000research.8245.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879932PMC
May 2016

Dissecting the cannabinergic control of behavior: The where matters.

Bioessays 2015 Nov 11;37(11):1215-25. Epub 2015 Aug 11.

Group "Endocannabinoids and Neuroadaptation," NeuroCentre Magendie, INSERM U862, University of Bordeaux, Bordeaux, France.

The endocannabinoid system is the target of the main psychoactive component of the plant Cannabis sativa, the Δ(9)-tetrahydrocannabinol (THC). This system is composed by the cannabinoid receptors, the endogenous ligands, and the enzymes involved in their metabolic processes, which works both centrally and peripherally to regulate a plethora of physiological functions. This review aims at explaining how the site-specific actions of the endocannabinoid system impact on memory and feeding behavior through the cannabinoid receptors 1 (CB1 R). Centrally, CB1 R is widely distributed in many brain regions, different cell types (e.g. neuronal or glial cells) and intracellular compartments (e.g. mitochondria). Interestingly, cellular and molecular effects are differentially mediated by CB1 R according to their cell-type localization (e.g. glutamatergic or GABAergic neurons). Thus, understanding the cellular and subcellular function of CB1 R will provide new insights and aid the design of new compounds in cannabinoid-based medicine. Also watch the Video Abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/bies.201500046DOI Listing
November 2015

Cannabinoid type 1 (CB1) receptors on Sim1-expressing neurons regulate energy expenditure in male mice.

Endocrinology 2015 Feb 2;156(2):411-8. Epub 2014 Dec 2.

Inserm (P.C., L.B., O.G.-Q., C.A., S.C., M.E., T.L.-L., D.G., A.C., G.M., D.C.) and Université de Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, unit 862, F-33000 Bordeaux, France; and Department of Biochemistry and Molecular Biology I and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) (L.B.), School of Biology, Complutense University-Instituto Universitario de Investigación Neuroquímica, 28040 Madrid, Spain.

The paraventricular nucleus of the hypothalamus (PVN) regulates energy balance by modulating not only food intake, but also energy expenditure (EE) and brown adipose tissue thermogenesis. To test the hypothesis that cannabinoid type 1 (CB1) receptor in PVN neurons might control these processes, we used the Cre/loxP system to delete CB1 from single-minded 1 (Sim1) neurons, which account for the majority of PVN neurons. On standard chow, mice lacking CB1 receptor in Sim1 neurons (Sim1-CB1-knockout [KO]) had food intake, body weight, adiposity, glucose metabolism, and EE comparable with wild-type (WT) (Sim1-CB1-WT) littermates. However, maintenance on a high-fat diet revealed a gene-by-diet interaction whereby Sim1-CB1-KO mice had decreased adiposity, improved insulin sensitivity, and increased EE, whereas feeding behavior was similar to Sim1-CB1-WT mice. Additionally, high-fat diet-fed Sim1-CB1-KO mice had increased mRNA expression of the β3-adrenergic receptor, as well as of uncoupling protein-1, cytochrome-c oxidase subunit IV and mitochondrial transcription factor A in the brown adipose tissue, all molecular changes suggestive of increased thermogenesis. Pharmacological studies using β-blockers suggested that modulation of β-adrenergic transmission play an important role in determining EE changes observed in Sim1-CB1-KO. Finally, chemical sympathectomy abolished the obesity-resistant phenotype of Sim1-CB1-KO mice. Altogether, these findings reveal a diet-dependent dissociation in the CB1 receptor control of food intake and EE, likely mediated by the PVN, where CB1 receptors on Sim1-positive neurons do not impact food intake but hinder EE during dietary environmental challenges that promote body weight gain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/en.2014-1437DOI Listing
February 2015

CB1 cannabinoid receptor in SF1-expressing neurons of the ventromedial hypothalamus determines metabolic responses to diet and leptin.

Mol Metab 2014 Oct 1;3(7):705-16. Epub 2014 Aug 1.

INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France ; University of Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France.

Metabolic flexibility allows rapid adaptation to dietary change, however, little is known about the CNS mechanisms regulating this process. Neurons in the hypothalamic ventromedial nucleus (VMN) participate in energy balance and are the target of the metabolically relevant hormone leptin. Cannabinoid type-1 (CB1) receptors are expressed in VMN neurons, but the specific contribution of endocannabinoid signaling in this neuronal population to energy balance regulation is unknown. Here we demonstrate that VMN CB1 receptors regulate metabolic flexibility and actions of leptin. In chow-fed mice, conditional deletion of CB1 in VMN neurons (expressing the steroidogenic factor 1, SF1) decreases adiposity by increasing sympathetic activity and lipolysis, and facilitates metabolic effects of leptin. Conversely, under high-fat diet, lack of CB1 in VMN neurons produces leptin resistance, blunts peripheral use of lipid substrates and increases adiposity. Thus, CB1 receptors in VMN neurons provide a molecular switch adapting the organism to dietary change.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molmet.2014.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209357PMC
October 2014

Early social enrichment rescues adult behavioral and brain abnormalities in a mouse model of fragile X syndrome.

Neuropsychopharmacology 2015 Mar 13;40(5):1113-22. Epub 2015 Mar 13.

1] Université Bordeaux, INCIA, Talence, France [2] CNRS, INCIA, UMR5287, Talence, France.

Converging lines of evidence support the use of environmental stimulation to ameliorate the symptoms of a variety of neurodevelopmental disorders. Applying these interventions at very early ages is critical to achieve a marked reduction of the pathological phenotypes. Here we evaluated the impact of early social enrichment in Fmr1-KO mice, a genetic mouse model of fragile X syndrome (FXS), a major developmental disorder and the most frequent monogenic cause of autism. Enrichment was achieved by providing male KO pups and their WT littermates with enhanced social stimulation, housing them from birth until weaning with the mother and an additional nonlactating female. At adulthood they were tested for locomotor, social, and cognitive abilities; furthermore, dendritic alterations were assessed in the hippocampus and amygdala, two brain regions known to be involved in the control of the examined behaviors and affected by spine pathology in Fmr1-KOs. Enrichment rescued the behavioral FXS-like deficits displayed in adulthood by Fmr1-KO mice, that is, hyperactivity, reduced social interactions, and cognitive deficits. Early social enrichment also eliminated the abnormalities shown by adult KO mice in the morphology of hippocampal and amygdala dendritic spines, namely an enhanced density of immature vs mature types. Importantly, enrichment did not induce neurobehavioral changes in WT mice, thus supporting specific effects on FXS-like pathology. These findings show that early environmental stimulation has profound and long-term beneficial effects on the pathological FXS phenotype, thereby encouraging the use of nonpharmacological interventions for the treatment of this and perhaps other neurodevelopmental diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/npp.2014.291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367453PMC
March 2015

New insights on food intake control by olfactory processes: the emerging role of the endocannabinoid system.

Mol Cell Endocrinol 2014 Nov 27;397(1-2):59-66. Epub 2014 Sep 27.

INSERM, U862 NeuroCentre Magendie, Endocannabinoids and Neuroadaptation, Bordeaux, France.

The internal state of the organism is an important modulator of perception and behavior. The link between hunger, olfaction and feeding behavior is one of the clearest examples of these connections. At the neurobiological level, olfactory circuits are the targets of several signals (i.e. hormones and nutrients) involved in energy balance. This indicates that olfactory areas are potential sensors of the internal state of the organism. Thus, the aim of this manuscript is to review the literature showing the interplay between metabolic signals in olfactory circuits and its impact on food intake.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mce.2014.09.023DOI Listing
November 2014