scholarly journals Dual Inhibition of FAAH and MAGL Counteracts Migraine-like Pain and Behavior in an Animal Model of Migraine

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2543
Author(s):  
Rosaria Greco ◽  
Chiara Demartini ◽  
Miriam Francavilla ◽  
Anna Maria Zanaboni ◽  
Cristina Tassorelli
Keyword(s):  
Gene Expression ◽  
Animal Model ◽  
Cervical Spinal Cord ◽  
Endocannabinoid System ◽  
Serum Levels ◽  
Cytokine Gene Expression ◽  
Dual Inhibitor ◽  
Vehicle Injection ◽  
Dual Inhibition ◽  
Cephalic Pain

The endocannabinoid system exerts an important role in pain processing and modulation. Modulation of the system with hydrolase inhibitors of anandamide (AEA) or 2-arachidonyl glycerol (2-AG) has proved effective in reducing migraine-like features in animal models of migraine. Here, we investigated the effect of dual inhibition of the AEA and 2-AG catabolic pathways in the nitroglycerin-based animal model of migraine. The dual inhibitor JZL195 was administered to rats 2 h after nitroglycerin or vehicle injection. Rats were then exposed to the open field test and the orofacial formalin test. At the end of the tests, they were sacrificed to evaluate calcitonin gene-related peptide (CGRP) serum levels and gene expression of CGRP and cytokines in the cervical spinal cord and the trigeminal ganglion. The dual inhibitor significantly reduced the nitroglycerin-induced trigeminal hyperalgesia and pain-associated behavior, possibly via cannabinoid 1 receptors-mediated action, but it did not change the hypomotility and the anxiety behaviors induced by nitroglycerin. The decreased hyperalgesia was associated with a reduction in CGRP and cytokine gene expression levels in central and peripheral structures and reduced CGRP serum levels. These data suggest an antinociceptive synergy of the endocannabinoid action in peripheral and central sites, confirming that this system participates in reduction of cephalic pain signals.

scholarly journals Alterations in Anandamide Synthesis and Degradation during Osteoarthritis Progression in an Animal Model

2020 ◽  
Vol 21 (19) ◽  
pp. 7381
Author(s):  
Marta Bryk ◽  
Jakub Chwastek ◽  
Magdalena Kostrzewa ◽  
Jakub Mlost ◽  
Aleksandra Pędracka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Animal Model ◽  
Endocannabinoid System ◽  
Joint Inflammation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Lumbar Spinal Cord ◽  
Trpv1 Receptors ◽  
Synthesis And Degradation

Osteoarthritis (OA) is a degenerative joint disease manifested by movement limitations and chronic pain. Endocannabinoid system (ECS) may modulate nociception via cannabinoid and TRPV1 receptors. The purpose of our study was to examine alterations in the spinal and joint endocannabinoid system during pain development in an animal model of OA. Wistar rats received intra-articular injection of 3mg of sodium monoiodoacetate (MIA) into the knee joint. Animals were sacrificed on day 2, 7, 14, 21, 28 after injection and lumbar spinal cord, cartilage and synovium were collected. Changes in the transcription levels of the ECS elements were measured. At the spinal level, gene expression levels of the cannabinoid and TRPV1 receptors as well as enzymes involved in anandamide synthesis and degradation were elevated in the advanced OA phase. In the joint, an important role of the synovium was demonstrated, since cartilage degeneration resulted in attenuation of the changes in the gene expression. Enzymes responsible for anandamide synthesis and degradation were upregulated particularly in the early stages of OA, presumably in response to early local joint inflammation. The presented study provides missing information about the MIA-induced OA model and encourages the development of a therapy focused on the molecular role of ECS.

Low Serum Levels of Fibroblast Growth Factor 2 in Gunn Rats: A Hyperbilirubinemia Animal Model of Schizophrenic Symptoms

2020 ◽  
Vol 19 (7) ◽  
pp. 503-508
Author(s):  
Maiko Hayashida ◽  
Sadayuki Hashioka ◽  
Kenji Hayashida ◽  
Shoko Miura ◽  
Keiko Tsuchie ◽  
...  
Keyword(s):  
Animal Model ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Wistar Rats ◽  
Serum Levels ◽  
Significant Negative Correlation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Normal Strain ◽  
Fibroblast Growth ◽  
Gunn Rats

Background: Fibroblast growth factor (FGF) 2 (also referred to as basic FGF) is a multifunctional growth factor that plays a pivotal role in the pro-survival, pro-migration and pro-differentiation of neurons. Method: Because alterations in FGF2 levels are suggested to contribute to the pathogenesis schizophrenia, we investigated serum levels of FGF2 in the Gunn rat, a hyperbilirubinemia animal model of schizophrenic symptoms. Results: The enzyme-linked immunosorbent assay showed that the serum levels of FGF2 in Gunn rats were 5.09 ± 0.236 pg/mL, while those in the normal strain Wistar rats were 11.90 ± 2.142 pg/mL. The serum FGF2 levels in Gunn rats were significantly lower than those in Wistar rats. We also measured serum levels of unconjugated bilirubin (UCB) and found a significant negative correlation between UCB and FGF2 at serum levels in all the rats studied. Conclusion: Since it is known that FGF2 regulates dopaminergic neurons and have anti-neuroinflammatory effects, our finding suggests that low FGF2 levels may contribute to the pathogenesis of schizophrenia, in which disbalanced dopamin-ergic signaling and neuroinflammation are supposed to play certain roles.

scholarly journals Cytokine gene expression in skin of susceptible guinea‐pig infected withTreponema pallidum

Immunology ◽  
1998 ◽  
Vol 95 (2) ◽  
pp. 242-247 ◽  
Author(s):  
WICHER ◽  
SCAROZZA ◽  
RAMSINGH ◽  
WICHER
Keyword(s):  
Gene Expression ◽  
Guinea Pig ◽  
Cytokine Gene Expression ◽  
Cytokine Gene

scholarly journals Epigenetic Regulation of Cytokine Gene Expression in T Lymphocytes

2009 ◽  
Vol 50 (3) ◽  
pp. 322 ◽  
Author(s):  
Choong-Gu Lee ◽  
Anupama Sahoo ◽  
Sin-Hyeog Im
Keyword(s):  
Gene Expression ◽  
T Lymphocytes ◽  
Epigenetic Regulation ◽  
Cytokine Gene Expression ◽  
Cytokine Gene

scholarly journals Endocannabinoid system mediates the association between gut-microbial diversity and anhedonia/amotivation in a general population cohort

2021 ◽  
Author(s):  
Amedeo Minichino ◽  
Matthew A. Jackson ◽  
Marta Francesconi ◽  
Claire J. Steves ◽  
Cristina Menni ◽  
...  
Keyword(s):  
General Population ◽  
Microbial Diversity ◽  
Gut Microbiome ◽  
Endocannabinoid System ◽  
Alpha Diversity ◽  
Serum Levels ◽  
Population Cohort ◽  
Random Intercept ◽  
General Population Cohort ◽  
Antidepressant Use

AbstractAnhedonia and amotivation are debilitating symptoms and represent unmet therapeutic needs in a range of clinical conditions. The gut-microbiome-endocannabinoid axis might represent a potential modifiable target for interventions. Based on results obtained from animal models, we tested the hypothesis that the endocannabinoid system mediates the association between gut-microbiome diversity and anhedonia/amotivation in a general population cohort. We used longitudinal data collected from 786 volunteer twins recruited as part the TwinsUK register. Our hypothesis was tested with a multilevel mediation model using family structure as random intercept. The model was set using alpha diversity (within-individual gut-microbial diversity) as predictor, serum and faecal levels of the endocannabinoid palmitoylethanolamide (PEA) as mediator, and anhedonia/amotivation as outcome. PEA is considered the endogenous equivalent of cannabidiol, with increased serum levels believed to have anti-depressive effects, while increased stool PEA levels, reflecting increased excretion, are believed to have opposite, detrimental, effects on mental health. We therefore expected that either reduced serum PEA or increased stool PEA would mediate the association between microbial diversity and anhedonia amotivation. Analyses were adjusted for obesity, diet, antidepressant use, sociodemographic and technical covariates. Data were imputed using multiple imputation by chained equations. Mean age was 65.2 ± 7.6; 93% of the sample were females. We found a direct, significant, association between alpha diversity and anhedonia/amotivation (β = −0.37; 95%CI: −0.71 to −0.03; P = 0.03). Faecal, but not serum, levels of the endocannabinoid palmitoylethanolamide (PEA) mediated this association: the indirect effect was significant (β = −0.13; 95%CI: −0.24 to −0.01; P = 0.03), as was the total effect (β = −0.38; 95%CI: −0.72 to −0.04; P = 0.03), whereas the direct effect of alpha diversity on anhedonia/amotivation was attenuated fully (β = −0.25; 95%CI: −0.60 to 0.09; P = 0.16). Our results suggest that gut-microbial diversity might contribute to anhedonia/amotivation via the endocannabinoid system. These findings shed light on the biological underpinnings of anhedonia/amotivation and suggest the gut microbiota-endocannabinoid axis as a promising therapeutic target in an area of unmet clinical need.

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