Neuroimmmune interactions of cannabinoids in neurogenesis: focus on interleukin-1β (IL-1β) signalling

2013 ◽  
Vol 41 (6) ◽  
pp. 1577-1582 ◽  
Author(s):  
Daniel García-Ovejero ◽  
Ángel Arévalo-Martín ◽  
Beatriz Navarro-Galve ◽  
Emmanuel Pinteaux ◽  
Eduardo Molina-Holgado ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cannabinoid Receptors ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Endocannabinoid System ◽  
Interleukin 1Β ◽  
Signalling Pathways ◽  
Brain Repair ◽  
Adult Nscs ◽  
The Brain

Neuroimmune networks and the brain endocannabinoid system contribute to the maintenance of neurogenesis. Activation of cannabinoid receptors suppresses chronic inflammatory responses through the attenuation of pro-inflammatory mediators. Moreover, the endocannabinoid system directs cell fate specification of NSCs (neural stem cells) in the CNS (central nervous sytem). The aim of our work is to understand better the relationship between the endocannabinoid and the IL-1β (interleukin-1β) associated signalling pathways and NSC biology, in order to develop therapeutical strategies on CNS diseases that may facilitate brain repair. NSCs express functional CB1 and CB2 cannabinoid receptors, DAGLα (diacylglycerol lipase α) and the NSC markers SOX-2 and nestin. We have investigated the role of CB1 and CB2 cannabinoid receptors in the control of NSC proliferation and in the release of immunomodulators [IL-1β and IL-1Ra (IL-1 receptor antagonist)] that control NSC fate decisions. Pharmacological blockade of CB1 and/or CB2 cannabinoid receptors abolish or decrease NSC proliferation, indicating a critical role for both CB1 and CB2 receptors in the proliferation of NSC via IL-1 signalling pathways. Thus the endocannabinoid system, which has neuroprotective and immunomodulatory actions mediated by IL-1 signalling cascades in the brain, could assist the process of proliferation and differentiation of embryonic or adult NSCs, and this may be of therapeutic interest in the emerging field of brain repair.

scholarly journals Cellular and intracellular mechanisms involved in the cognitive impairment of cannabinoids

2012 ◽  
Vol 367 (1607) ◽  
pp. 3254-3263 ◽  
Author(s):  
Emma Puighermanal ◽  
Arnau Busquets-Garcia ◽  
Rafael Maldonado ◽  
Andrés Ozaita
Keyword(s):  
Cognitive Function ◽  
Molecular Mechanisms ◽  
Cannabinoid Receptors ◽  
Critical Role ◽  
Mammalian Target Of Rapamycin ◽  
Endocannabinoid System ◽  
Protein Translation ◽  
Signalling Pathways ◽  
Cellular Processes ◽  
Extracellular Signal

Exogenous cannabinoids, such as delta9-tetrahydrocannabinol (THC), as well as the modulation of endogenous cannabinoids, affect cognitive function through the activation of cannabinoid receptors. Indeed, these compounds modulate a number of signalling pathways critically implicated in the deleterious effect of cannabinoids on learning and memory. Thus, the involvement of the mammalian target of rapamycin pathway and extracellular signal-regulated kinases, together with their consequent regulation of cellular processes such as protein translation, play a critical role in the amnesic-like effects of cannabinoids. In this study, we summarize the cellular and molecular mechanisms reported in the modulation of cognitive function by the endocannabinoid system.

Endocannabinoid-Mediated Control of Synaptic Transmission

2009 ◽  
Vol 89 (1) ◽  
pp. 309-380 ◽  
Author(s):  
Masanobu Kano ◽  
Takako Ohno-Shosaku ◽  
Yuki Hashimotodani ◽  
Motokazu Uchigashima ◽  
Masahiko Watanabe
Keyword(s):  
Synaptic Transmission ◽  
Intracellular Signaling ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Brain Regions ◽  
New Era ◽  
Behavioral Studies ◽  
Electrophysiological Studies ◽  
The Brain ◽  
Subsequent Identification

The discovery of cannabinoid receptors and subsequent identification of their endogenous ligands (endocannabinoids) in early 1990s have greatly accelerated research on cannabinoid actions in the brain. Then, the discovery in 2001 that endocannabinoids mediate retrograde synaptic signaling has opened up a new era for cannabinoid research and also established a new concept how diffusible messengers modulate synaptic efficacy and neural activity. The last 7 years have witnessed remarkable advances in our understanding of the endocannabinoid system. It is now well accepted that endocannabinoids are released from postsynaptic neurons, activate presynaptic cannabinoid CB1 receptors, and cause transient and long-lasting reduction of neurotransmitter release. In this review, we aim to integrate our current understanding of functions of the endocannabinoid system, especially focusing on the control of synaptic transmission in the brain. We summarize recent electrophysiological studies carried out on synapses of various brain regions and discuss how synaptic transmission is regulated by endocannabinoid signaling. Then we refer to recent anatomical studies on subcellular distribution of the molecules involved in endocannabinoid signaling and discuss how these signaling molecules are arranged around synapses. In addition, we make a brief overview of studies on cannabinoid receptors and their intracellular signaling, biochemical studies on endocannabinoid metabolism, and behavioral studies on the roles of the endocannabinoid system in various aspects of neural functions.

Cannabinoids and the Brain

2017 ◽  
Author(s):  
Linda A. Parker
Keyword(s):  
Cannabinoid Receptors ◽  
Legal Status ◽  
Therapeutic Potential ◽  
Scientific Discovery ◽  
Scientific Evidence ◽  
Endocannabinoid System ◽  
Preclinical Research ◽  
Pain Anxiety ◽  
Scientific Investigations ◽  
The Brain

Cannabinoids and the Brain introduces an informed general audience to the scientific discovery of the endocannabinoid system and recent preclinical research that explains its importance in brain functioning. The endocannabinoids, anandamide and 2-AG, act on the same cannabinoid receptors, that are activated by the primary psychoactive compound found in marijuana, Δ‎9-tetrahydrocannabinol (THC). Therefore, the scientific investigations of the functions of the endocannabinoid system are guided by the known effects of marijuana on the brain and body. The book reviews the scientific evidence of the role that the endocannabinoid system plays in regulating emotion, anxiety, depression, psychosis, reward and addiction, learning and memory, feeding, nausea/vomiting, pain, epilepsy, and other neurological disorders. Anecdotal reports are linked with the current scientific literature on the medicinal benefits of marijuana. Cannabis contains over 80 chemicals that have closely related structures, called cannabinoids, but the only major mood-altering constituent is THC. Another major plant cannabinoid is cannabidiol (CBD), which is not psychoactive; yet, considerable recent preclinical research reviewed in various chapters reveals that CBD has promising therapeutic potential in treatment of pain, anxiety, nausea and epilepsy. Only recently, has research been conducted with some of the other compounds found in cannabis. The subject matter of the book is extremely timely in light of the current ongoing debate not only about medical marijuana, but also about its legal status.

Endocannabinoids and Food Intake: Newborn Suckling and Appetite Regulation in Adulthood

2005 ◽  
Vol 230 (4) ◽  
pp. 225-234 ◽  
Author(s):  
Ester Fride ◽  
Tatyana Bregman ◽  
Tim C. Kirkham
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Cannabinoid Receptors ◽  
Cannabis Sativa ◽  
Critical Role ◽  
Growth Failure ◽  
Endocannabinoid System ◽  
Failure To Thrive ◽  
Receptor Activation ◽  
Organ Systems

The appetite-stimulating effects of the cannabis plant (Cannabis sativa) have been known since ancient times, and appear to be effected through the incentive and rewarding properties of foods. Investigations into the biological basis of the multiple effects of cannabis have yielded important breakthroughs in recent years: the discovery of two cannabinoid receptors in brain and peripheral organ systems, and endogenous ligands (endocannabinoids) for these receptors. These advances have greatly increased our understanding of how appetite is regulated through these endocannabinoid receptor systems. The presence of endocannabinoids in the developing brain and in maternal milk have led to evidence for a critical role for CB, receptors in oral motor control of suckling during neonatal development. The endocannabinoids appear to regulate energy balance and food intake at four functional levels within the brain and periphery: (i) limbic system (for hedonic evaluation of foods), (ii) hypothalamus and hindbrain (integrative functions), (iii) intestinal system, and (iv) adipose tissue. At each of these levels, the endocannabinoid system interacts with a number of better known molecules involved in appetite and weight regulation, including leptin, ghrelin, and the melanocortins. Therapeutically, appetite stimulation by cannabinoids has been studied for several decades, particularly in relation to cachexia and malnutrition associated with cancer, acquired immunodeficiency syndrome, or anorexia nervosa. The recent advances in cannabinoid pharmacology may lead to improved treatments for these conditions or, conversely, for combating excessive appetite and body weight, such as CB, receptor antagonists as antiobesity medications. In conclusion, the exciting progress in the understanding of how the endocannabinoid CB receptor systems influence appetite and body weight is stimulating the development of therapeutic orexigenic and anorectic agents. Furthermore, the role of cannabinoid CB, receptor activation for milk suckling in newborns may open new doors toward understanding nonorganic failure-to-thrive in infants, who display growth failure without known organic cause.

scholarly journals IL2 Neural stem cell regulation and brain development

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi1-vi1
Author(s):  
Yukiko Gotoh
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Underlying Mechanism ◽  
Ependymal Cells ◽  
Stem Cell Regulation ◽  
Cycle Arrest ◽  
Adult Nscs ◽  
Neural Stem Progenitor Cells ◽  
The Brain

Abstract Quiescent neural stem cells (NSCs) in the adult mouse brain are the source of neurogenesis that regulates innate and adaptive behaviors. Adult NSCs in the subventricular zone (SVZ) are derived from a subpopulation of embryonic neural stem-progenitor cells (NPCs) that is characterized by a slower cell cycle relative to the more abundant rapid cycling NPCs that build the brain. We have previously shown that slow cell cycle can cause the establishment of adult NSCs at the SVZ, although the underlying mechanism remains unknown. We found that Notch and an effector Hey1 form a module that is upregulated by cell cycle arrest in slowly dividing NPCs. In contrast to the oscillatory expression of the Notch effectors Hes1 and Hes5 in fast cycling progenitors, Hey1 displays a non-oscillatory stationary expression pattern and contributes to the long-term maintenance of NSCs. These findings reveal a novel division of labor in Notch effectors where cell cycle rate biases effector selection and cell fate. I will also discuss the heterogeneity of slowly dividing embryonic NPCs and the lineage relationship between adult NSCs and ependymal cells, which together form the niche for adult neurogenesis at the SVZ.

scholarly journals A Brief Background on Cannabis: From Plant to Medical Indications

2019 ◽  
Vol 102 (2) ◽  
pp. 412-420 ◽  
Author(s):  
Linda E Klumpers ◽  
David L Thacker
Keyword(s):  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Good Evidence ◽  
The Body ◽  
Post Traumatic Stress ◽  
History Of ◽  
Post Traumatic ◽  
Loss Of Appetite ◽  
Medical Indications ◽  
The Brain

Abstract Cannabis has been used as a medicinal plant for thousands of years. As a result of centuries of breeding and selection, there are now over 700 varieties of cannabis that contain hundreds of compounds, including cannabinoids and terpenes. Cannabinoids are fatty compounds that are the main biological active constituents of cannabis. Terpenes are volatilecompounds that occur in many plants and have distinct odors. Cannabinoids exert their effect on the body by binding to receptors, specifically cannabinoid receptors types 1 and 2. These receptors, together with endogenous cannabinoids and the systems forsynthesis, transport, and degradation, are called the Endocannabinoid System. The two most prevalent and commonly known cannabinoids in the cannabis plantare delta-9-tetrahydrocannabinol (THC) and cannabidiol. The speed, strength, and type of effects of cannabis vary based on the route of administration. THC is rapidly distributed through the body to fattytissues like the brain and is metabolized by the cytochrome P450 system to 11-hydroxy-THC, which is also psychoactive. Cannabis and cannabinoids have been indicated for several medical conditions. There is evidence of efficacy in the symptomatic treatmentof nausea and vomiting, pain, insomnia, post-traumatic stress disorder, anxiety, loss of appetite, Tourette’s syndrome, and epilepsy. Cannabis hasalso been associated with treatment for glaucoma, Huntington’s Disease, Parkinson’s Disease, and dystonia, but thereis not good evidence tosupport its efficacy. Side effects of cannabis include psychosis and anxiety, which can be severe. Here, we provided a summary ofthe history of cannabis,its pharmacology, and its medical uses.

scholarly journals Targeting Cannabinoid Receptors: Current Status and Prospects of Natural Products

2020 ◽  
Vol 21 (14) ◽  
pp. 5064 ◽  
Author(s):  
Dongchen An ◽  
Steve Peigneur ◽  
Louise Antonia Hendrickx ◽  
Jan Tytgat
Keyword(s):  
Natural Products ◽  
Cannabinoid Receptors ◽  
Structural Information ◽  
Critical Role ◽  
Synthetic Cannabinoids ◽  
Endocannabinoid System ◽  
Current Status ◽  
Therapeutic Effects ◽  
Drug Leads

Cannabinoid receptors (CB1 and CB2), as part of the endocannabinoid system, play a critical role in numerous human physiological and pathological conditions. Thus, considerable efforts have been made to develop ligands for CB1 and CB2, resulting in hundreds of phyto- and synthetic cannabinoids which have shown varying affinities relevant for the treatment of various diseases. However, only a few of these ligands are clinically used. Recently, more detailed structural information for cannabinoid receptors was revealed thanks to the powerfulness of cryo-electron microscopy, which now can accelerate structure-based drug discovery. At the same time, novel peptide-type cannabinoids from animal sources have arrived at the scene, with their potential in vivo therapeutic effects in relation to cannabinoid receptors. From a natural products perspective, it is expected that more novel cannabinoids will be discovered and forecasted as promising drug leads from diverse natural sources and species, such as animal venoms which constitute a true pharmacopeia of toxins modulating diverse targets, including voltage- and ligand-gated ion channels, G protein-coupled receptors such as CB1 and CB2, with astonishing affinity and selectivity. Therefore, it is believed that discovering novel cannabinoids starting from studying the biodiversity of the species living on planet earth is an uncharted territory.

scholarly journals Interaction between Cannabinoid System and Toll-Like Receptors Controls Inflammation

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Kathleen L. McCoy
Keyword(s):  
Pattern Recognition ◽  
Immune Cells ◽  
Innate Immune System ◽  
Cannabinoid Receptors ◽  
Inflammatory Responses ◽  
Endocannabinoid System ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Toll Like Receptor ◽  
Receptor Family

Since the discovery of the endocannabinoid system consisting of cannabinoid receptors, endogenous ligands, and biosynthetic and metabolizing enzymes, interest has been renewed in investigating the promise of cannabinoids as therapeutic agents. Abundant evidence indicates that cannabinoids modulate immune responses. An inflammatory response is triggered when innate immune cells receive a danger signal provided by pathogen- or damage-associated molecular patterns engaging pattern-recognition receptors. Toll-like receptor family members are prominent pattern-recognition receptors expressed on innate immune cells. Cannabinoids suppress Toll-like receptor-mediated inflammatory responses. However, the relationship between the endocannabinoid system and innate immune system may not be one-sided. Innate immune cells express cannabinoid receptors and produce endogenous cannabinoids. Hence, innate immune cells may play a role in regulating endocannabinoid homeostasis, and, in turn, the endocannabinoid system modulates local inflammatory responses. Studies designed to probe the interaction between the innate immune system and the endocannabinoid system may identify new potential molecular targets in developing therapeutic strategies for chronic inflammatory diseases. This review discusses the endocannabinoid system and Toll-like receptor family and evaluates the interaction between them.

scholarly journals Different Dietary n-3 Polyunsaturated Fatty Acid Formulations Distinctively Modify Fatty Acid and N-Acylethanolamine Profiles in Rat Brain

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 349-349
Author(s):  
Elisabetta Murru ◽  
Gianfranca Carta ◽  
Armita Abolghasemi ◽  
Claudia Manca ◽  
José AM Prates ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Soybean Oil ◽  
Cannabinoid Receptors ◽  
Partial Agonist ◽  
Linseed Oil ◽  
Endocannabinoid System ◽  
Funding Sources ◽  
Epa And Dha ◽  
The Central Nervous System ◽  
The Brain

Abstract Objectives Dietary n-3 polyunsaturated fatty acids (n-3PUFA) may influence the brain fatty acid (FA) profile and, thereby, the biosynthesis of FA bioactive metabolite, such as N-acylethanolamines (NAE). We investigated the influence of different dietary formulation of n-3PUFA from vegetable or marine oils on rat FA incorporation and modulation of NAE biosynthesis. Methods Rats were fed for 10 weeks with diets containing 12% of fat from milk + 4% soybean oil and 4% of oils with different n-3 PUFA species: soybean oil as control (MilkFat), linseed oil with α-linolenic (ALA) (LSO), Buglossoides arvensis oil with ALA and stearidonic (SDA) (Buglos), fish oil with EPA and DHA (FO), Nannochloropsis microalga oil with EPA (Nanno) or Schizochytrium microalga oil with DHA (Schy). Brain FA and NAE profile were assessed LC-DAD-MS/MS. Statistical Kruskal-Wallis test followed by Dunn's correction was applied. Results Different dietary n-3PUFA formulations induced FA change in the brain, compared to MilkFat group, DHA levels remained unchanged despite its elevated intake with FO and Schy diets. However, we found 9 fold (P < 0.001) increase of EPA with FO, arachidonic (AA) decreased significantly about 16% (P < 0.05) with LSO and FO diets. n-6 PUFA docosatetraenoic (DTA) (26% P < 0.05) and docosapentaenoic (DPA) (73% P < 0.05) were reduced with FO, probably due to a competition with EPA in the incorporation into phospholipids. We observed a 44% (P < 0.05) significant decrease of N-arachidonoylethanolamine (AEA) with LSO and FO, and a reduction of N-linoleoylethanolamine (LEA) by 49% (P < 0.05) with LSO. On the other hand, we found an increase of N-eicosapentanoylethanolamine (EPEA), derived from EPA, by 225% (P < 0.05) with FO, compared to MilkFat group. Conclusions Our data indicate that reduction of AEA levels might attenuate its effects on the CB1 cannabinoid receptors, the main molecular target of the endogenous partial agonist AEA, which regulate physiological processes in the central nervous system. Therefore, in those pathophysiological conditions where is desirable to downregulate an overactive endocannabinoid system, a mixture of EPA and DHA as in FO, and ALA as in LSO, may potentially be a preferred nutritional source of n-3 PUFA. Funding Sources University of Cagliari (FIR 2019) and Fundação FCT (Portugal).

scholarly journals Hippocampal Cb2 receptors: an untold story

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Robin Visvanathar ◽  
Maria Papanikolaou ◽  
Diana Aline Nôga ◽  
Marina Pádua-Reis ◽  
Adriano Bretanha Lopes Tort ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Wide Distribution ◽  
Significant Progress ◽  
Medical Cannabis ◽  
Functional Roles ◽  
The Central Nervous System ◽  
Cb2 Receptors ◽  
The Brain ◽  
Insight Into

Abstract The field of cannabinoid research has been receiving ever-growing interest. Ongoing debates worldwide about the legislation of medical cannabis further motivates research into cannabinoid function within the central nervous system (CNS). To date, two well-characterized cannabinoid receptors exist. While most research has investigated Cb1 receptors (Cb1Rs), Cb2 receptors (Cb2Rs) in the brain have started to attract considerable interest in recent years. With indisputable evidence showing the wide-distribution of Cb2Rs in the brain of different species, they are no longer considered just peripheral receptors. However, in contrast to Cb1Rs, the functionality of central Cb2Rs remains largely unexplored. Here we review recent studies on hippocampal Cb2Rs. While conflicting results about their function have been reported, we have made significant progress in understanding the involvement of Cb2Rs in modulating cellular properties and network excitability. Moreover, Cb2Rs have been shown to be expressed in different subregions of the hippocampus, challenging our prior understanding of the endocannabinoid system. Although more insight into their functional roles is necessary, we propose that targeting hippocampal Cb2Rs may offer novel therapies for diseases related to memory and adult neurogenesis deficits.

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