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.

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 Bioactive Chemical Composition of Cannabis Extracts and Cannabinoid Receptors

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3466 ◽  
Author(s):  
Yi Yang ◽  
Rupali Vyawahare ◽  
Melissa Lewis-Bakker ◽  
Hance A. Clarke ◽  
Albert H. C. Wong ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Therapeutic Drug ◽  
Chemical Compositions ◽  
Least Squares Regression ◽  
Medical Cannabis ◽  
Cb2 Receptors ◽  
The Relationship

Cannabis is widely used as a therapeutic drug, especially by patients suffering from psychiatric and neurodegenerative diseases. However, the complex interplay between phytocannabinoids and their targets in the human receptome remains largely a mystery, and there have been few investigations into the relationship between the chemical composition of medical cannabis and the corresponding biological activity. In this study, we investigated 59 cannabis samples used by patients for medical reasons. The samples were subjected to extraction (microwave and supercritical carbon dioxide) and chemical analyses, and the resulting extracts were assayed in vitro using the CB1 and CB2 receptors. Using a partial least squares regression analysis, the chemical compositions of the extracts were then correlated to their corresponding cannabinoid receptor activities, thus generating predictive models that describe the receptor potency as a function of major phytocannabinoid content. Using the current dataset, meaningful models for CB1 and CB2 receptor agonism were obtained, and these reveal the insignificant relationships between the major phytocannabinoid content and receptor affinity for CB1 but good correlations between the two at CB2 receptors. These results also explain the anomalies between the receptor activities of pure phytocannabinoids and cannabis extracts. Furthermore, the models for CB1 and CB2 agonism in cannabis extracts predict the cannabinoid receptor activities of individual phytocannabinoids with reasonable accuracy. Here for the first time, we disclose a method to predict the relationship between the chemical composition, including phytocannabinoids, of cannabis extracts and cannabinoid receptor responses.

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.

scholarly journals New Insights Into Peptide Cannabinoids: Structure, Biosynthesis and Signaling

2020 ◽  
Vol 11 ◽  
Author(s):  
Agustín Riquelme-Sandoval ◽  
Caio O. de Sá-Ferreira ◽  
Leo M. Miyakoshi ◽  
Cecilia Hedin-Pereira
Keyword(s):  
Fatty Acid ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Current Knowledge ◽  
Physiological Role ◽  
Endocannabinoid System ◽  
Peripheral Tissues ◽  
New Family ◽  
Peptide Family ◽  
The Central Nervous System

Classically, the endocannabinoid system (ECS) consists of endogenous lipids, of which the best known are anandamide (AEA) and 2 arachidonoylglycerol (2-AG), their enzyme machinery for synthesis and degradation and their specific receptors, cannabinoid receptor one (CB1) and cannabinoid receptor two (CB2). However, endocannabinoids also bind to other groups of receptors. Furthermore, another group of lipids are considered to be endocannabinoids, such as the fatty acid ethanolamides, the fatty acid primary amides and the monoacylglycerol related molecules. Recently, it has been shown that the hemopressin peptide family, derived from α and β chains of hemoglobins, is a new family of cannabinoids. Some studies indicate that hemopressin peptides are expressed in the central nervous system and peripheral tissues and act as ligands of these receptors, thus suggesting that they play a physiological role. In this review, we examine new evidence on lipid endocannabinoids, cannabinoid receptors and the modulation of their signaling pathways. We focus our discussion on the current knowledge of the pharmacological effects, the biosynthesis of the peptide cannabinoids and the new insights on the activation and modulation of cannabinoid receptors by these peptides. The novel peptide compounds derived from hemoglobin chains and their non-classical activation of cannabinoid receptors are only starting to be uncovered. It will be exciting to follow the ensuing discoveries, not only in reference to what is already known of the classical lipid endocannabinoids revealing more complex aspects of endocannabinoid system, but also as to its possibilities as a future therapeutic tool.

scholarly journals Purinergic Receptors of the Central Nervous System: Biology, PET Ligands, and Their Applications

2020 ◽  
Vol 19 ◽  
pp. 153601212092760
Author(s):  
Hamideh Zarrinmayeh ◽  
Paul R. Territo
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Purinergic Receptors ◽  
P2y Receptors ◽  
Cns Disorders ◽  
Extracellular Adenosine ◽  
Functional Roles ◽  
Positron Emission ◽  
The Central Nervous System ◽  
The Brain

Purinergic receptors play important roles in central nervous system (CNS). These receptors are involved in cellular neuroinflammatory responses that regulate functions of neurons, microglial and astrocytes. Based on their endogenous ligands, purinergic receptors are classified into P1 or adenosine, P2X and P2Y receptors. During brain injury or under pathological conditions, rapid diffusion of extracellular adenosine triphosphate (ATP) or uridine triphosphate (UTP) from the damaged cells, promote microglial activation that result in the changes in expression of several of these receptors in the brain. Imaging of the purinergic receptors with selective Positron Emission Tomography (PET) radioligands has advanced our understanding of the functional roles of some of these receptors in healthy and diseased brains. In this review, we have accumulated a list of currently available PET radioligands of the purinergic receptors that are used to elucidate the receptor functions and participations in CNS disorders. We have also reviewed receptors lacking radiotracer, laying the foundation for future discoveries of novel PET radioligands to reveal these receptors roles in CNS disorders.

scholarly journals Endocannabinoids in neuroendopsychology: multiphasic control of mitochondrial function

2012 ◽  
Vol 367 (1607) ◽  
pp. 3342-3352 ◽  
Author(s):  
Alistair Nunn ◽  
Geoffrey Guy ◽  
Jimmy D. Bell
Keyword(s):  
Mitochondrial Function ◽  
Metabolic Pathways ◽  
Endocannabinoid System ◽  
Positive Energy ◽  
Positive Energy Balance ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Insight Into ◽  
Subsequent Identification

The endocannabinoid system (ECS) is a construct based on the discovery of receptors that are modulated by the plant compound tetrahydrocannabinol and the subsequent identification of a family of nascent ligands, the ‘endocannabinoids’. The function of the ECS is thus defined by modulation of these receptors—in particular, by two of the best-described ligands (2-arachidonyl glycerol and anandamide), and by their metabolic pathways. Endocannabinoids are released by cell stress, and promote both cell survival and death according to concentration. The ECS appears to shift the immune system towards a type 2 response, while maintaining a positive energy balance and reducing anxiety. It may therefore be important in resolution of injury and inflammation. Data suggest that the ECS could potentially modulate mitochondrial function by several different pathways; this may help explain its actions in the central nervous system. Dose-related control of mitochondrial function could therefore provide an insight into its role in health and disease, and why it might have its own pathology, and possibly, new therapeutic directions.

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.

scholarly journals The Endocannabinoid System in the Retina: From Physiology to Practical and Therapeutic Applications

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Thomas Schwitzer ◽  
Raymund Schwan ◽  
Karine Angioi-Duprez ◽  
Anne Giersch ◽  
Vincent Laprevote
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cannabinoid Receptors ◽  
Synthetic Cannabinoids ◽  
Endocannabinoid System ◽  
Main Role ◽  
Cannabinoid System ◽  
Retinal Processing ◽  
The Central Nervous System ◽  
The Impact

Cannabisis one of the most prevalent drugs used in industrialized countries. The main effects ofCannabisare mediated by two major exogenous cannabinoids: ∆9-tetrahydroxycannabinol and cannabidiol. They act on specific endocannabinoid receptors, especially types 1 and 2. Mammals are endowed with a functional cannabinoid system including cannabinoid receptors, ligands, and enzymes. This endocannabinoid signaling pathway is involved in both physiological and pathophysiological conditions with a main role in the biology of the central nervous system. As the retina is a part of the central nervous system due to its embryonic origin, we aim at providing the relevance of studying the endocannabinoid system in the retina. Here, we review the distribution of the cannabinoid receptors, ligands, and enzymes in the retina and focus on the role of the cannabinoid system in retinal neurobiology. This review describes the presence of the cannabinoid system in critical stages of retinal processing and its broad involvement in retinal neurotransmission, neuroplasticity, and neuroprotection. Accordingly, we support the use of synthetic cannabinoids as new neuroprotective drugs to prevent and treat retinal diseases. Finally, we argue for the relevance of functional retinal measures in cannabis users to evaluate the impact of cannabis use on human retinal processing.

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 Restriction of Manganese Intake Prevents the Onset of Brain Manganese Overload in Zip14−/− Mice

2021 ◽  
Vol 22 (13) ◽  
pp. 6773
Author(s):  
Yuze Wu ◽  
Guojun Wei ◽  
Ningning Zhao
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Small Intestine ◽  
Neurological Disorders ◽  
The Body ◽  
Future Studies ◽  
The Central Nervous System ◽  
Manganese Transport ◽  
The Brain ◽  
Insight Into

As a newly identified manganese transport protein, ZIP14 is highly expressed in the small intestine and liver, which are the two principal organs involved in regulating systemic manganese homeostasis. Loss of ZIP14 function leads to manganese overload in both humans and mice. Excess manganese in the body primarily affects the central nervous system, resulting in irreversible neurological disorders. Therefore, to prevent the onset of brain manganese accumulation becomes critical. In this study, we used Zip14−/− mice as a model for ZIP14 deficiency and discovered that these mice were born without manganese loading in the brain, but started to hyper-accumulate manganese within 3 weeks after birth. We demonstrated that decreasing manganese intake in Zip14−/− mice was effective in preventing manganese overload that typically occurs in these animals. Our results provide important insight into future studies that are targeted to reduce the onset of manganese accumulation associated with ZIP14 dysfunction in humans.

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