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Special Issue "Endocannabinoid System in Health and Disease: Current Situation and Future Perspectives"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 31 October 2019.

Special Issue Editor

Guest Editor
Dr. Rosaria Meccariello Website E-Mail
Department of Movement and Wellness Sciences, Parthenope University of Naples, Via Medina 40, I-80133 Naples, Italy
Interests: Endocannabinoid system; Endocannabinoids-GnRH-steroids crosstalk; Kisspeptins; reproduction; HPG axis, spermatogenesis; spermatozoa; endocrine disruptors; epigenetics

Special Issue Information

Dear Colleagues,

The discovery of the endocannabinoid system (ECS) comprising cannabinoid receptors, their endogenous ligands (endocannabinoids), and synthetic and metabolizing enzymes triggered a large number of studies in cell lines, animal models, and humans. ECS modulates many physiological and pathological processes, both in the peripheral and central nervous systems and in peripheral organs. This signaling system has a recognized activity on nervous system development, synaptic plasticity, learning and memory, neuroinflammation, pain and neurodegeneration, stress responsivity, mood and behavior, food intake and metabolism, reproduction, fertility and pregnancy, immune response, cardiac functions, cancer progression, and so much more. As a consequence, the modulation of ECS signaling has potential therapeutic applications for a broad range of diseases, including neurodegenerative, reproductive, cardiovascular, and inflammatory disorders, metabolic syndrome and obesity, and cancer, among many others. However, despite experimental evidence, molecular and epigenetic regulatory mechanisms of ECS activity remain to be fully elucidated, hence the need to fill this gap in order to devise clinically successful treatment strategies.

This Special issue aims at expanding the current knowledge on ECS in both physiological and pathological conditions and on its possible therapeutic exploitation. Experimental studies in in vitro and in vivo models, review articles, and clinical studies as well are all welcome for consideration.

Dr. Rosaria Meccariello
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • endocannabinoids
  • endocannabinoids system
  • synaptic plasticity
  • neurological diseases
  • energy balance, food intake and metabolic disorders
  • reproduction, fertility and pregnancy
  • immune response
  • cardiac functions
  • stress
  • pain
  • cancer progression

Published Papers (3 papers)

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Research

Open AccessArticle
Different Routes to Inhibit Fatty Acid Amide Hydrolase: Do All Roads Lead to the Same Place?
Int. J. Mol. Sci. 2019, 20(18), 4503; https://doi.org/10.3390/ijms20184503 - 11 Sep 2019
Abstract
There is robust evidence indicating that enhancing the endocannabinoid (eCB) tone has therapeutic potential in several brain disorders. The inhibition of eCBs degradation by fatty acid amide hydrolase (FAAH) blockade, is the best-known option to increase N-acyl-ethanolamines-(NAEs)-mediated signaling. Here, we investigated the [...] Read more.
There is robust evidence indicating that enhancing the endocannabinoid (eCB) tone has therapeutic potential in several brain disorders. The inhibition of eCBs degradation by fatty acid amide hydrolase (FAAH) blockade, is the best-known option to increase N-acyl-ethanolamines-(NAEs)-mediated signaling. Here, we investigated the hypothesis that intranasal delivery is an effective route for different FAAH inhibitors, such as URB597 and PF-04457845. URB597 and PF-04457845 were subchronically administered in C57BL/6 male mice every other day for 20 days for overall 10 drug treatment, and compared for their ability to inhibit FAAH activity by the way of three different routes of administration: intranasal (i.n.), intraperitoneal (i.p.) and oral (p.o.). Lastly, we compared the efficacy of the three routes in terms of URB597-induced increase of NAEs levels in liver and in different brain areas. Results: We show that PF-04457845 potently inhibits FAAH regardless the route selected, and that URB597 was less effective in the brain after p.o. administration while reached similar effects by i.n. and i.p. routes. Intranasal URB597 delivery always increased NAEs levels in brain areas, whereas a parallel increase was not observed in the liver. By showing the efficacy of intranasal FAAH inhibition, we provide evidence that nose-to-brain delivery is a suitable alternative to enhance brain eCB tone for the treatment of neurodegenerative disorders and improve patients’ compliance. Full article
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Open AccessCommunication
Stable Adult Hippocampal Neurogenesis in Cannabinoid Receptor CB2 Deficient Mice
Int. J. Mol. Sci. 2019, 20(15), 3759; https://doi.org/10.3390/ijms20153759 - 01 Aug 2019
Abstract
The G-protein coupled cannabinoid receptor 2 (CB2) has been implicated in the regulation of adult neurogenesis in the hippocampus. The contribution of CB2 towards basal levels of proliferation and the number of neural progenitors in the subgranular zone (SGZ) of the dentate gyrus, [...] Read more.
The G-protein coupled cannabinoid receptor 2 (CB2) has been implicated in the regulation of adult neurogenesis in the hippocampus. The contribution of CB2 towards basal levels of proliferation and the number of neural progenitors in the subgranular zone (SGZ) of the dentate gyrus, however, remain unclear. We stained hippocampal brain sections of 16- to 17-week-old wildtype and CB2-deficient mice, for neural progenitor and immature neuron markers doublecortin (DCX) and calretinin (CR) and for the proliferation marker Ki67 and quantified the number of positive cells in the SGZ. The quantification revealed that CB2 deficiency neither altered overall cell proliferation nor the size of the DCX+ or DCX and CR double-positive populations in the SGZ compared to control animals. The results indicate that CB2 might not contribute to basal levels of adult neurogenesis in four-month-old healthy mice. CB2 signaling might be more relevant in conditions where adult neurogenesis is dynamically regulated, such as neuroinflammation. Full article
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Open AccessArticle
Role of Major Endocannabinoid-Binding Receptors during Mouse Oocyte Maturation
Int. J. Mol. Sci. 2019, 20(12), 2866; https://doi.org/10.3390/ijms20122866 - 12 Jun 2019
Abstract
Endocannabinoids are key-players of female fertility and potential biomarkers of reproductive dysfunctions. Here, we investigated localization and expression of cannabinoid receptor type-1 and -2 (CB1R and CB2R), G-protein coupled receptor 55 (GPR55), and transient receptor potential vanilloid type 1 [...] Read more.
Endocannabinoids are key-players of female fertility and potential biomarkers of reproductive dysfunctions. Here, we investigated localization and expression of cannabinoid receptor type-1 and -2 (CB1R and CB2R), G-protein coupled receptor 55 (GPR55), and transient receptor potential vanilloid type 1 channel (TRPV1) in mouse oocytes collected at different stages of in vivo meiotic maturation (germinal vesicle, GV; metaphase I, MI; metaphase II, MII) through qPCR, confocal imaging, and western blot. Despite the significant decrease in CB1R, CB2R, and GPR55 mRNAs occurring from GV to MII, CB2R and GPR55 protein contents increased during the same period. At GV, only CB1R was localized in oolemma, but it completely disappeared at MI. TRPV1 was always undetectable. When oocytes were in vitro matured with CB1R and CB2R but not GPR55 antagonists, a significant delay of GV breakdown occurred, sustained by elevated intraoocyte cAMP concentration. Although CBRs antagonists did not affect polar body I emission or chromosome alignment, GPR55 antagonist impaired in ~75% of oocytes the formation of normal-sized MI and MII spindles. These findings open a new avenue to interrogate oocyte pathophysiology and offer potentially new targets for the therapy of reproductive alterations. Full article
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