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Karasu T.,University of Leicester | Marczylo T.H.,University of Leicester | Maccarrone M.,University of Teramo | Maccarrone M.,European Center for Brain Research | Konje J.C.,University of Leicester
Human Reproduction Update | Year: 2011

Background: Marijuana, the most used recreational drug, has been shown to have adverse effects on human reproduction. Endogenous cannabinoids (also called endocannabinoids) bind to the same receptors as those of Δ9-tetrahydrocannabinol (THC), the psychoactive component of Cannabis sativa. The most extensively studied endocannabinoids are anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol. The endocannabinoids, their congeners and the cannabinoid receptors, together with the metabolic enzymes and putative transporters form the endocannabinoid system (ECS). In this review, we summarize current knowledge about the relationships of ECS, sex steroid hormones and cytokines in female fertility, and underline the importance of this endocannabinoid-hormone-cytokine network. Methods: Pubmed and the Web of Science databases were searched for studies published since 1985, looking into the ECS, sex hormones, type-1/2 T-helper (Th1/Th2) cytokines, leukaemia inhibitory factor, leptin and reproduction. Results: The ECS plays a pivotal role in human reproduction. The enzymes involved in the synthesis and degradation of endocannabinoids normalize levels of AEA for successful implantation. The AEA degrading enzyme (fatty acid amide hydrolase) activity as well as AEA content in blood may potentially be used for the monitoring of early pregnancies. Progesterone and oestrogen are involved in the maintenance of endocannabinoid levels. The ECS plays an important role in the immune regulation of human fertility. Conclusions: The available studies suggest that tight control of the endocannabinoid-hormone-cytokine network is required for successful implantation and early pregnancy maintenance. This hormone-cytokine network is a key element at the maternal-foetal interface, and any defect in such a network may result in foetal loss. © The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. Source

MacCarrone M.,University of Teramo | MacCarrone M.,European Center for Brain Research | Gasperi V.,University of Rome Tor Vergata | Catani M.V.,University of Rome Tor Vergata | And 4 more authors.
Annual Review of Nutrition | Year: 2010

Endocannabinoids bind to cannabinoid, vanilloid, and peroxisome proliferator-activated receptors. The biological actions of these polyunsaturated lipids are controlled by key agents responsible for their synthesis, transport and degradation, which together form an endocannabinoid system (ECS). In the past few years, evidence has been accumulated for a role of the ECS in regulating food intake and energy balance, both centrally and peripherally. In addition, up-regulation of the ECS in the gastrointestinal tract has a potential impact on lammatory bowel diseases. In this review, the main features of the ECS are summarized in order to put in better focus our current knowledge of the nutritional relevance of endocannabinoid signaling and of its role in obesity, cardiovascular pathologies, and gastrointestinal diseases. The central and peripheral pathways that underlie these effects are discussed, as well as the possible exploitation of ECS components as novel drug targets for therapeutic intervention in eating disorders. Copyright © 2010 by Annual Reviews. All rights reserved. Source

Carola V.,Mouse Biology Unit | Carola V.,European Center for Brain Research | Gross C.,Mouse Biology Unit
Genes, Brain and Behavior | Year: 2010

Anxiety is known to be influenced by both adverse childhood experiences and genetic susceptibility factors. A polymorphism in the brain-derived neurotrophic factor (BDNF) gene modulates the association between adverse early experiences and risk for anxiety and depression in adulthood. An animal model of this gene-by-environment risk factor is lacking. Using two different early environmental manipulations, we found that a heterozygous null mutation in the mouse BDNF gene moderated the long-term effect of maternal care on innate anxiety behavior. Although changes in maternal care were associated with mild changes in anxiety in wild-type mice, this effect was magnified in heterozygous null BDNF mice with high-and low-maternal care associated with low and high levels, respectively, of avoidance behavior as measured in the open field and elevated plus maze tests. These data argue for an increased sensitivity to early environmental influences of mice with reduced BDNF function and support the important role of this neurotrophic factor in the developmental plasticity of brain circuits controlling anxiety. © 2010 Blackwell Publishing Ltd/International Behavioural and Neural Genetics Society. Source

Chiurchiu V.,European Center for Brain Research
Current Topics in Medicinal Chemistry | Year: 2014

Despite multiple sclerosis (MS) represents one of the most fascinating mystery of modern medicine due to its unknown etiology and the incomplete knowledge of a clear mechanism of pathogenesis, progress against this disease has made giant leaps. Current management of MS takes advantage of many disease- modifying therapeutics of anti-inflammatory and immunomodulatory nature, whose primary aims are halting immune responses during attacks, preventing new attacks and avoiding disability. In this review, a synopsis on effective therapies targeting both immune-mediated responses and neurodegenerative processes is appointed. Oxidative stress has been also implicated in both the inflammatory and neurodegenerative pathological mechanisms underlying MS. The role of redox metabolism in MS is thus also reported, with particular focus on the latest improvements in the identification of oxidative stress as a potential new therapeutic target. © 2014 Bentham Science Publishers. Source

D'Addario C.,University of Teramo | D'Addario C.,Karolinska Institutet | Micioni Di Bonaventura M.V.,University of Camerino | Pucci M.,University of Teramo | And 6 more authors.
Neuroscience and Biobehavioral Reviews | Year: 2014

Overeating, frequently linked to an increasing incidence of overweight and obesity, has become epidemic and one of the leading global health problems. To explain the development of this eating behavior, new hypotheses involve the concept that many people might be addicted to food by losing control over their ability to regulate food intake. Among the different neurotransmitter networks that partake in the reward circuitry within the brain, a large body of evidence supports the involvement of the endocannabinoid system. Indeed, its dysfunctions might contribute to food addiction, by regulating appetite and food preference through central and peripheral mechanisms. Here, we review and discuss the role of endocannabinoid signaling in the reward circuitry, and the possible therapeutic exploitation of strategies based on its fine regulation. © 2014 Elsevier Ltd. Source

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