Endocannabinoids and the haematological system.
Ontology highlight
ABSTRACT:
SUBMITTER: Randall MD
PROVIDER: S-EPMC2190025 | biostudies-other | 2007 Nov
REPOSITORIES: biostudies-other
Similar Datasets
Project description:The endocannabinoid (eCB) system has been implicated in a variety of physiological functions due to abundant expression of its receptors and endogenous ligands in the central nervous system. Substantial progress has been made in understanding how the eCB system influences the brain norepinephrine (NE) system, an important neurochemical target in the continued development of new therapies for stress-induced psychiatric disorders. We, and others, have characterized the neuroanatomical, biochemical and pharmacological effects of cannabinoid receptor modulation on brain noradrenergic circuitry and defined how molecular elements of the eCB system are positioned to directly impact the locus coeruleus (LC)-prefrontal cortex pathway, a neural circuit well recognized for contributing to symptoms of hyperarousal, a key pathophysiological feature of stress-related disorders. We also described molecular and electrophysiological properties of LC noradrenergic neurons and NE release in the medial prefrontal cortex under conditions of cannabinoid type 1 receptor deletion. Finally, we identified how stress influences cannabinoid modulation of the coeruleo-cortical pathway. A number of significant findings emerged from these studies that will be summarized in the present review and have important implications for clinical studies targeting the eCB system in the treatment of stress-induced psychiatric disorders.
| S-EPMC6582240 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver morbidity and mortality with no proven effective therapy as of yet. Its prevalence is increasing globally in parallel with obesity and metabolic syndrome pandemic. The endocannabinoid (EC) system has been implicated in the pathogenesis of several diseases, including fatty liver diseases. This system refers to the cannabinoid receptors type 1 (CB1) and type 2 (CB2), with both their endogenous ligands and machinery dedicated to EC synthesis and degradation. There is accumulating evidence on the role CB1 as a key mediator of insulin resistance and liver lipogenesis in both animals and humans. On the other hand, CB2 receptors have been shown to promote inflammation with anti-fibrogenic properties. The pharmacological modulation of the EC system activity for the treatment of metabolic syndrome and NAFLD are promising yet premature. The initial limited success due to deleterious central nervous system side-effects are likely to be bypassed with the use of peripherally restricted drugs.
| S-EPMC3745655 | biostudies-other
Project description:The endocannabinoids anandamide and 2-arachydonoylglycerol (2-AG) are lipids naturally derived from membrane precursors which bind cannabinoid receptors (CB1, CB2). This endocannabinoid system is disturbed in schizophrenia. Indeed, there seems to be an association between schizophrenia and polymorphisms of the CB1 receptor gene. Moreover, CB1 receptors are found in higher density in the prefrontal cortex, hippocampus and basal ganglia of patients with schizophrenia. Similarly, anandamide levels are increased in the cerebrospinal fluid (CSF) and in the serum of schizophrenia patients, including during the prodromal state, suggesting that they may play a protective role in psychosis homeostasis. Future studies are needed to further explore the role of the endocannabinoid system in the pathophysiology of schizophrenia.
| S-EPMC4034083 | biostudies-literature
Project description:BackgroundActivation of the endocannabinoid system (ECS) is associated with the development of obesity and insulin resistance, and with perturbed skeletal muscle development. Age-related sarcopenia is a progressive and generalized skeletal muscle disorder involving an accelerated loss of muscle mass and function, with changes in skeletal muscle protein homeostasis due to lipid accumulation and anabolic resistance. Hence, both obesity and sarcopenia share a common set of pathophysiological alterations leading to skeletal muscle impairment. The aim of this study was to characterize how sarcopenia impacts the ECS and if these modifications were related to the loss of muscle mass and function associated with aging in rats.MethodsSix-month-old and 24-month-old male rats were used to measure the contractile properties of the plantarflexors (isometric torque-frequency relationship & concentric power-velocity relationship) and to evaluate locomotor activity, motor coordination, and voluntary gait by open field, rotarod, and catwalk tests, respectively. Levels of endocannabinoids (AEA & 2-AG) and endocannabinoid-like molecules (OEA & PEA) were measured by LCF-MS/MS in plasma, skeletal muscle, and adipose tissue, while the expression of genes coding for the ECS were investigated by quantitative reverse transcription PCR (RT-qPCR).ResultsSarcopenia in old rats was exemplified by a 49% decrease in hindlimb muscle mass (P < 0.01), which was associated with severe impairment of isometric torque, power, voluntary locomotor activity, motor coordination, and gait quality. Sarcopenia was associated with (1) increased 2-AG (+32%, P = 0.07) and reduced PEA and OEA levels in the plasma (-25% and -40%, respectively, P < 0.01); (2) an increased content of AEA, PEA, and OEA in subcutaneous adipose tissue (P < 0.01); and (3) a four-fold increase of 2-AG content in the soleus (P < 0.01) and a reduced OEA content in EDL (-80%, P < 0.01). These alterations were associated with profound modifications in the expression of the ECS genes in the adipose tissue and skeletal muscle.ConclusionsTaken together, these findings demonstrate that circulating and peripheral tissue endocannabinoid tone are altered in sarcopenia. They also demonstrate that OEA plasma levels are associated with skeletal muscle function and loss of locomotor activity in rats, suggesting OEA could be used as a circulating biomarker for sarcopenia.
| S-EPMC8818601 | biostudies-literature
Project description:Traumatic brain injury (TBI) represents the leading cause of death in young individuals. It triggers the accumulation of harmful mediators, leading to secondary damage, yet protective mechanisms are also set in motion. The endocannabinoid (eCB) system consists of ligands, such as anandamide and 2-arachidonoyl-glycerol (2-AG), receptors (e.g. CB1, CB2), transporters and enzymes, which are responsible for the 'on-demand' synthesis and degradation of these lipid mediators. There is a large body of evidence showing that eCB are markedly increased in response to pathogenic events. This fact, as well as numerous studies on experimental models of brain toxicity, neuroinflammation and trauma supports the notion that the eCB are part of the brain's compensatory or repair mechanisms. These are mediated via CB receptors signalling pathways that are linked to neuronal survival and repair. The levels of 2-AG, the most highly abundant eCB, are significantly elevated after TBI and when administered to TBI mice, 2-AG decreases brain oedema, inflammation and infarct volume and improves clinical recovery. The role of CB1 in mediating these effects was demonstrated using selective antagonists or CB1 knockout mice. CB2 were shown in other models of brain insults to reduce white blood cell rolling and adhesion, to reduce infarct size and to improve motor function. This review is focused on the role the eCB system plays as a self-neuroprotective mechanism and its potential as a basis for the development of novel therapeutic modality for the treatment of CNS pathologies with special emphasis on TBI.
| S-EPMC3165950 | biostudies-literature
Project description:Endocannabinoids such as anandamide [N-arachidonoylethanolamine (AEA)] and 2-arachidonoyl glycerol (2-AG) are known orexigenic mediators that act via CB(1) receptors in hypothalamus and limbic forebrain to induce appetite and stimulate food intake. Circulating endocannabinoid levels inversely correlate with plasma levels of leptin, an anorexigenic mediator that reduces food intake by acting on hypothalamic receptors. Recently, taste has been found to be a peripheral target of leptin. Leptin selectively suppresses sweet taste responses in wild-type mice but not in leptin receptor-deficient db/db mice. Here, we show that endocannabinoids oppose the action of leptin to act as enhancers of sweet taste. We found that administration of AEA or 2-AG increases gustatory nerve responses to sweeteners in a concentration-dependent manner without affecting responses to salty, sour, bitter, and umami compounds. The cannabinoids increase behavioral responses to sweet-bitter mixtures and electrophysiological responses of taste receptor cells to sweet compounds. Mice genetically lacking CB(1) receptors show no enhancement by endocannnabinoids of sweet taste responses at cellular, nerve, or behavioral levels. In addition, the effects of endocannabinoids on sweet taste responses of taste cells are diminished by AM251, a CB(1) receptor antagonist, but not by AM630, a CB(2) receptor antagonist. Immunohistochemistry shows that CB(1) receptors are expressed in type II taste cells that also express the T1r3 sweet taste receptor component. Taken together, these observations suggest that the taste organ is a peripheral target of endocannabinoids. Reciprocal regulation of peripheral sweet taste reception by endocannabinoids and leptin may contribute to their opposing actions on food intake and play an important role in regulating energy homeostasis.
| S-EPMC2818929 | biostudies-literature
Project description:CB1 cannabinoid receptors are expressed on vagal afferent fibers and neurons within the solitary tract nucleus (NTS), providing anatomical evidence for their role in arterial baroreflex modulation. To better understand the relationship between the brain renin-angiotensin system (RAS) and endocannabinoid expression within the NTS, we measured dorsal medullary endocannabinoid tissue content and the effects of CB1 receptor blockade at this brain site on cardiac baroreflex sensitivity (BRS) in ASrAOGEN rats with low glial angiotensinogen, normal Sprague-Dawley rats and (mRen2)27 rats with upregulated brain RAS expression. Mass spectrometry revealed higher levels of the endocannabinoid 2-arachidonoylglycerol in (mRen2)27 compared to ASrAOGEN rats (2.70 ± 0.28 vs. 1.17 ± 0.09 ng/mg tissue; P < 0.01), while Sprague-Dawley rats had intermediate content (1.85 ± 0.27 ng/mg tissue). Microinjection of the CB1receptor antagonist SR141716A (36 pmol) into the NTS did not change cardiac BRS in anesthetized Sprague-Dawley rats (1.04 ± 0.05 ms/mmHg baseline vs. 1.17 ± 0.11 ms/mmHg after 10 min). However, SR141716A in (mRen2)27 rats dose-dependently improved BRS in this strain: 0.36 pmol of SR141716A increased BRS from 0.43 ± 0.03 to 0.71 ± 0.04 ms/mmHg (P < 0.001), and 36 pmol of SR141716A increased BRS from 0.47 ± 0.02 to 0.94 ± 0.10 ms/mmHg (P < 0.01). In contrast, 0.36 pmol (1.50 ± 0.12 vs. 0.86 ± 0.08 ms/mmHg; P < 0.05) and 36 pmol (1.38 ± 0.16 vs. 0.46 ± 0.003 ms/mmHg; P < 0.01) of SR141716A significantly reduced BRS in ASrAOGEN rats. These observations reveal differential dose-related effects of the brain endocannabinoid system that influence cardiovagal BRS in animals with genetic alterations in the brain RAS.
| S-EPMC4899471 | biostudies-literature
Project description:DNA methylation patterns are disrupted in various malignancies, suggesting a role in the development of cancer, but genetic aberrations directly linking the DNA methylation machinery to malignancies were rarely observed, so this association remained largely correlative. Recently, however, mutations in the gene encoding DNA methyltransferase 3A (DNMT3A) were reported in patients with acute myeloid leukaemia (AML), and subsequently in patients with various other haematological malignancies, pointing to DNMT3A as a critically important new tumour suppressor. Here, we review the clinical findings related to DNMT3A, tie these data to insights from basic science studies conducted over the past 20 years and present a roadmap for future research that should advance the agenda for new therapeutic strategies.
| S-EPMC5814392 | biostudies-literature
Project description:Our purpose was to compile information on the haematological manifestations of systemic lupus erythematosus (SLE), namely leucopenia, lymphopenia, thrombocytopenia, autoimmune haemolytic anaemia (AIHA), thrombotic thrombocytopenic purpura (TTP) and myelofibrosis. During our search of the English-language MEDLINE sources, we did not place a date-of-publication constraint. Hence, we have reviewed previous as well as most recent studies with the subject heading SLE in combination with each manifestation. Neutropenia can lead to morbidity and mortality from increased susceptibility to infection. Severe neutropenia can be successfully treated with granulocyte colony-stimulating factor. While related to disease activity, there is no specific therapy for lymphopenia. Severe lymphopenia may require the use of prophylactic therapy to prevent select opportunistic infections. Isolated idiopathic thrombocytopenic purpura maybe the first manifestation of SLE by months or even years. Some manifestations of lupus occur more frequently in association with low platelet count in these patients, for example, neuropsychiatric manifestation, haemolytic anaemia, the antiphospholipid syndrome and renal disease. Thrombocytopenia can be regarded as an important prognostic indicator of survival in patients with SLE. Medical, surgical and biological treatment modalities are reviewed for this manifestation. First-line therapy remains glucocorticoids. Through our review, we conclude glucocorticoids do produce a response in majority of patients initially, but sustained response to therapy is unlikely. Glucocorticoids are used as first-line therapy in patients with SLE with AIHA, but there is no conclusive evidence to guide second-line therapy. Rituximab is promising in refractory and non-responding AIHA. TTP is not recognised as a criteria for classification of SLE, but there is a considerable overlap between the presenting features of TTP and SLE, and a few patients with SLE have concurrent TTP. Myelofibrosis is an uncommon yet well-documented manifestation of SLE. We have compiled the cases that were reported in MEDLINE sources.
| S-EPMC4378375 | biostudies-literature
Project description:Endocannabinoids (ECBs) are ubiquitous lipid mediators that act through the same G protein-coupled receptors (CB1 and CB2) that recognize plant-derived cannabinoids. As regulators of metabolism, ECBs are anabolic: they increase the intake, promote the storage, and decrease the expenditure of energy. Recent work indicates that activation of peripheral CB1 receptors by ECBs plays a key role in the hormonal/metabolic changes associated with obesity/metabolic syndrome and may be targeted for its pharmacotherapy.
| S-EPMC2586261 | biostudies-literature