The role of cannabinoids in shaping lifespan neurodevelopment.
Ontology highlight
ABSTRACT:
SUBMITTER: Marusak HA
PROVIDER: S-EPMC10236571 | biostudies-literature | 2022 Mar
REPOSITORIES: biostudies-literature
Publications
The role of cannabinoids in shaping lifespan neurodevelopment.
Journal of neuroscience research 20220202 3
Similar Datasets
Project description:Fetal neurodevelopment in utero is profoundly shaped by both systemic maternal immunity and local processes at the maternal-fetal interface. Immune pathways are a critical participant in the normal physiology of pregnancy and perturbations of maternal immunity due to infections during this period have been increasingly linked to a diverse array of poor neurological outcomes, including diseases that manifest much later in postnatal life. While experimental models of maternal immune activation (MIA) have provided groundbreaking characterizations of the maternal pathways underlying pathogenesis, less commonly examined are the immune factors that serve pathogen-independent developmental functions in the embryo and fetus. In this review, we explore what is known about the in vivo role of immune factors in fetal neurodevelopment during normal pregnancy and provide an overview of how MIA perturbs the proper orchestration of this sequence of events. Finally, we discuss how the dysregulation of immune factors may contribute to the manifestation of a variety of neurological disorders.
| S-EPMC9034439 | biostudies-literature
Project description:Development of a neuron critically depends on the organization of its cytoskeleton. Cytoskeletal components, such as tubulins and actins, have the remarkable ability to organize themselves into filaments and networks to support specialized and compartmentalized functions. Alterations in cytoskeletal proteins have long been associated with a variety of neurodevelopmental disorders. This review focuses on recent findings, primarily from forward genetic screens in Caenorhabditis elegans that illustrate how different tubulin protein isotypes can play distinct roles in neuronal development and function. Additionally, we discuss studies revealing new regulators of the actin cytoskeleton, and highlight recent technological advances in in vivo imaging and functional dissection of the neuronal cytoskeleton.
| S-EPMC6066413 | biostudies-literature
Project description:Obesity is an increasing health problem worldwide. Its related comorbidities imply a high cost for the National Health System and diminish a patient's life quality. Adipose tissue is composed of three types of cells. White adipocytes are involved in fat storage and secretion of hormones. Brown adipocytes are involved in thermogenesis and caloric expenditure. Beige adipocytes are transitional adipocytes that in response to various stimuli can turn from white to brown and could be protective against the obesity, enhancing energy expenditure. The conversion of white in beige adipose tissue is a potential new therapeutic target for obesity. Cannabinoid receptors (CB) regulate thermogenesis, food intake and inflammation. CB1 ablation or inhibition helps reducing body weight and food intake. Stimulation of CB2 limits inflammation and promotes anti-obesity effects by reducing food intake and weight gain. Its genetic ablation results in adiposity development. CB receptors are also responsible for transforming white adipose tissue towards beige or brown adipocytes, therefore their modulation can be considered potential anti-obesity target. CB1 principal localization in central nervous system represents an important limit. Stimulation of CB2, principally localized on peripheral cells instead, should facilitate the anti-obesity effects without exerting remarkable psychotropic activity.
| S-EPMC6163475 | biostudies-literature
Project description:PTEN is a lipid and protein phosphatase that regulates cell growth and survival. Mutations to PTEN are highly penetrant for autism spectrum disorder (ASD). Here, we briefly review the evidence linking PTEN mutations to ASD and the mouse models that have been used to study the role of PTEN in neurodevelopment. We then focus on the cellular phenotypes associated with PTEN loss in neurons, highlighting the role PTEN plays in neuronal proliferation, migration, survival, morphology, and plasticity.
| S-EPMC7206585 | biostudies-literature
Project description:One of the main unanswered questions regarding the early steps of macroautophagy/autophagy is the mechanism of membrane-modeling events required for autophagosome formation. Three independent studies have recently revealed an actin cytoskeleton involvement in this process, providing significant details regarding the role of actin in nucleation events both inside and outside the phagophore membrane during its expansion and assembly.
| S-EPMC5173263 | biostudies-literature
Project description:Modulating the activity of the endocannabinoid system influences various gastrointestinal physiological and pathophysiological processes, and cannabinoid receptors as well as regulatory enzymes responsible for the synthesis or degradation of endocannabinoids representing potential targets to reduce the development of gastrointestinal mucosal lesions, hemorrhage and inflammation. Direct activation of CB1 receptors by plant-derived, endogenous or synthetic cannabinoids effectively reduces both gastric acid secretion and gastric motor activity, and decreases the formation of gastric mucosal lesions induced by stress, pylorus ligation, nonsteroidal anti-inflammatory drugs (NSAIDs) or alcohol, partly by peripheral, partly by central mechanisms. Similarly, indirect activation of cannabinoid receptors through elevation of endocannabinoid levels by globally acting or peripherally restricted inhibitors of their metabolizing enzymes (FAAH, MAGL) or by inhibitors of their cellular uptake reduces the gastric mucosal lesions induced by NSAIDs in a CB1 receptor-dependent fashion. Dual inhibition of FAAH and cyclooxygenase enzymes induces protection against both NSAID-induced gastrointestinal damage and intestinal inflammation. Moreover, in intestinal inflammation direct or indirect activation of CB1 and CB2 receptors exerts also multiple beneficial effects. Namely, activation of both CB receptors was shown to ameliorate intestinal inflammation in various murine colitis models, to decrease visceral hypersensitivity and abdominal pain, as well as to reduce colitis-associated hypermotility and diarrhea. In addition, CB1 receptors suppress secretory processes and also modulate intestinal epithelial barrier functions. Thus, experimental data suggest that the endocannabinoid system represents a promising target in the treatment of inflammatory bowel diseases, and this assumption is also confirmed by preliminary clinical studies.
| S-EPMC5333598 | biostudies-literature
Project description:BackgroundSil1 is the causative gene of Marinesco-Sjӧgren Syndrome (MSS). The mutated Sil1 generates shortened SIL1 protein which will form aggregation and be degraded rapidly. Mental retardation is a major symptom of MSS which suggests a role of SIL1 in the development of the central nervous system, but how SIL1 functions remains unclear.ObjectivesThe aim of this study is to explore the role of SIL1 in regulating cerebral development and its underlying molecular mechanism.MethodsThe basic expression pattern of SIL1 in tissues and cultured cortical neurons is measured by immunostaining and Western blot. The expression of SIL1 is reduced in vitro and in vivo through RNA interference delivered by a lentivirus. The expression of NMDA receptor subunits and the function of the Reelin signaling pathway are then examined by surface biotinylation and Western blot subsequently. Finally, the spatial learning of young mice was assessed by the Barnes maze task.ResultsSIL1 deficiency caused a diminished expression of both Reelin receptors and therefore impaired the Reelin signaling pathway. It then inhibited the developmental expression of GluN2A and impaired the spatial learning of 5-week-old mice.ConclusionsThese results suggested that SIL1 is required for the development of the central nervous system which is associated with its role in Reelin signaling.
| S-EPMC6720716 | biostudies-literature
Project description:The endocannabinoid system, including endogenous ligands ('endocannabinoids' ECs), their receptors, synthesizing and degrading enzymes, as well as transporter molecules, has been detected from the earliest stages of embryonic development and throughout pre- and postnatal development. ECs are bioactive lipids, which comprise amides, esters and ethers of long chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol (2-AG) are the best studied ECs, and act as agonists of cannabinoid receptors. Thus, AEA and 2-AG mimic several pharmacological effects of the exogenous cannabinoid delta9-tetrahydrocannabinol (Delta(9)-THC), the psychoactive principle of cannabis sativa preparations like hashish and marijuana. Recently, however, several lines of evidence have suggested that the EC system may play an important role in early neuronal development as well as a widespread role in neurodegeneration disorders. Many of the effects of cannabinoids and ECs are mediated by two G protein-coupled receptors (GPCRs), CB1 and CB2, although additional receptors may be implicated. Both CB1 and CB2 couple primarily to inhibitory G proteins and are subject to the same pharmacological influences as other GPCRs. This new system is briefly presented in this review, in order to put in a better perspective the role of the EC pathway from neurodevelopment to neurodegenerative disorders, like Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. In addition, the potential exploitation of antagonists of CB1 receptors, or of inhibitors of EC metabolism, as next-generation therapeutics is discussed.
| S-EPMC4739730 | biostudies-literature
Project description:The calcium/calmodulin-dependent protein kinase type 2 (CAMK2) family consists of four different isozymes, encoded by four different genes-CAMK2A, CAMK2B, CAMK2G, and CAMK2D-of which the first three have been associated recently with neurodevelopmental disorders. CAMK2D is one of the major CAMK2 proteins expressed in the heart and has been associated with cardiac anomalies. Although this CAMK2 isoform is also known to be one of the major CAMK2 subtypes expressed during early brain development, it has never been linked with neurodevelopmental disorders until now. Here we show that CAMK2D plays an important role in neurodevelopment not only in mice but also in humans. We identified eight individuals harboring heterozygous variants in CAMK2D who display symptoms of intellectual disability, delayed speech, behavioral problems, and dilated cardiomyopathy. The majority of the variants tested lead to a gain of function (GoF), which appears to cause both neurological problems and dilated cardiomyopathy. In contrast, loss-of-function (LoF) variants appear to induce only neurological symptoms. Together, we describe a cohort of individuals with neurodevelopmental disorders and cardiac anomalies, harboring pathogenic variants in CAMK2D, confirming an important role for the CAMK2D isozyme in both heart and brain function.
| S-EPMC10870144 | biostudies-literature
Project description:Cannabinoids are a group of chemicals that bind to receptors in the human body and, in turn, modulate the endocannabinoid system (ECS). They can be endogenously produced, synthetic, or derived from the plant Cannabis sativa L. Research over the past several decades has shown that the ECS is a cellular communication network essential to maintain multiple biological functions and the homeostasis of the body. Indeed, cannabinoids have been shown to influence a wide variety of biological effects, including memory, pain, reproduction, bone remodeling or immunity, to name a few. Unsurprisingly, given these broad physiological effects, alterations of the ECS have been found in different diseases, including cancer. In recent years, the medical use of cannabis has been approved in different countries for a variety of human conditions. However, the use of these compounds, specifically as anticancer agents, remains controversial. Studies have shown that cannabinoids do have anticancer activity in different tumor types such as breast cancer, melanoma, lymphoma and adult brain cancer. Specifically, phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) has been shown to induce apoptosis and inhibit proliferation of adult cancer cells, as well as modulate angiogenesis and metastasis. Despite increasing evidence that cannabinoids elicit antitumor effects in adult cancers, there is minimal data available on their effects in children or in pediatric cancers despite public and clinical demand for information. Here we describe a comprehensive and critical review of what is known about the effects of cannabinoids on pediatric cancers, highlight current gaps in knowledge and identify the critical issues that need addressing before considering these promising but controversial drugs for use in pediatric oncology.
| S-EPMC7796497 | biostudies-literature