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On the Role of Central Type-1 Cannabinoid Receptor Gene Regulation in Food Intake and Eating Behaviors.

ABSTRACT: Different neuromodulatory systems are involved in long-term energy balance and body weight and, among these, evidence shows that the endocannabinoid system, in particular the activation of type-1 cannabinoid receptor, plays a key role. We here review current literature focusing on the role of the gene encoding type-1 cannabinoid receptors in the CNS and on the modulation of its expression by food intake and specific eating behaviors. We point out the importance to further investigate how environmental cues might have a role in the development of obesity as well as eating disorders through the transcriptional regulation of this gene in order to prevent or to treat these pathologies.

SUBMITTER: Pucci M

PROVIDER: S-EPMC7796374 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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On the Role of Central Type-1 Cannabinoid Receptor Gene Regulation in Food Intake and Eating Behaviors.

Pucci Mariangela M Zaplatic Elizabeta E Micioni Di Bonaventura Maria Vittoria MV Micioni Di Bonaventura Emanuela E De Cristofaro Paolo P Maccarrone Mauro M Cifani Carlo C D'Addario Claudio C

International journal of molecular sciences 20210101 1

Different neuromodulatory systems are involved in long-term energy balance and body weight and, among these, evidence shows that the endocannabinoid system, in particular the activation of type-1 cannabinoid receptor, plays a key role. We here review current literature focusing on the role of the gene encoding type-1 cannabinoid receptors in the CNS and on the modulation of its expression by food intake and specific eating behaviors. We point out the importance to further investigate how environ ...[more]

PMID: 33401515

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Project description:Peripheral neuropathy is a major dose-limiting toxicity of chemotherapy, especially after multiple courses of paclitaxel. The development of paclitaxel-induced neuropathy is associated with the activation of microglia followed by the activation and proliferation of astrocytes, and the expression and release of proinflammatory cytokines in the spinal dorsal horn. Cannabinoid type 2 (CB(2)) receptors are expressed in the microglia in neurodegenerative disease models.To explore the potential of CB(2) agonists for preventing paclitaxel-induced neuropathy, we designed and synthesized a novel CB(2)-selective agonist, namely, MDA7. The effect of MDA7 in preventing paclitaxel-induced allodynia was assessed in rats and in CB(2)(+/+) and CB(2)(-/-) mice. We hypothesized that the CB(2) receptor functions in a negative-feedback loop and that early MDA7 administration can blunt the neuroinflammatory response to paclitaxel and prevent mechanical allodynia through interference with specific signaling pathways.We found that MDA7 prevents paclitaxel-induced mechanical allodynia in rats and mice in a dose- and time-dependent manner without compromising paclitaxel's antineoplastic effect. MDA7's neuroprotective effect was absent in CB(2)(-/-) mice and was blocked by CB(2) antagonists, suggesting that MDA7's action directly involves CB(2) receptor activation. MDA7 treatment was found to interfere with early events in the paclitaxel-induced neuroinflammatory response as evidenced by relatively reduced toll-like receptor and CB(2) expression in the lumbar spinal cord, reduced levels of extracellular signal-regulated kinase 1/2 activity, reduced numbers of activated microglia and astrocytes, and reduced secretion of proinflammatory mediators in vivo and in in vitro models.Our findings suggest an innovative therapeutic approach to prevent chemotherapy-induced neuropathy and may permit more aggressive use of active chemotherapeutic regimens with reduced long-term sequelae.

Dataset Information

On the Role of Central Type-1 Cannabinoid Receptor Gene Regulation in Food Intake and Eating Behaviors.

Publications

On the Role of Central Type-1 Cannabinoid Receptor Gene Regulation in Food Intake and Eating Behaviors.

Similar Datasets

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