THC and CBD: Similarities and differences between siblings

Neuron, Journal Year: 2023, Volume and Issue: 111(3), P. 302 - 327

Published: Jan. 12, 2023

---

Astrocytes as a Therapeutic Target in Alzheimer’s Disease–Comprehensive Review and Recent Developments

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(21), P. 13630 - 13630

Published: Nov. 7, 2022

Alzheimer’s disease (AD) is a frequent and disabling neurodegenerative disorder, in which astrocytes participate several pathophysiological processes including neuroinflammation, excitotoxicity, oxidative stress lipid metabolism (along with critical role apolipoprotein E function). Current evidence shows that have both neuroprotective neurotoxic effects depending on the stage microenvironmental factors. Furthermore, appear to be affected by presence of amyloid-beta (Aβ), alterations calcium levels, gliotransmission proinflammatory activity via RAGE-NF-κB pathway. In addition, play an important tau clearance Aβ through glymphatic system. this review, we will discuss novel pharmacological non-pharmacological treatments focused as therapeutic targets for AD. These interventions include anti-inflammatory/antioxidant systems, glutamate activity, metabolism, neurovascular coupling system, dysregulation, release peptides affects glial neuronal function. According AD stage, these therapies may benefit either preventing or delaying progression disease.

Language: Английский

---

Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 9067 - 9067

Published: May 22, 2023

Alzheimer’s disease (AD) is a chronic neurodegenerative and the most frequent cause of progressive dementia in senior adults. It characterized by memory loss cognitive impairment secondary to cholinergic dysfunction N-methyl-D-aspartate (NMDA)-mediated neurotoxicity. Intracellular neurofibrillary tangles, extracellular plaques composed amyloid-β (Aβ), selective neurodegeneration are anatomopathological hallmarks this disease. The dysregulation calcium may be present all stages AD, it associated with other pathophysiological mechanisms, such as mitochondrial failure, oxidative stress, neuroinflammation. Although cytosolic alterations AD not completely elucidated, some calcium-permeable channels, transporters, pumps, receptors have been shown involved at neuronal glial levels. In particular, relationship between glutamatergic NMDA receptor (NMDAR) activity amyloidosis has widely documented. Other mechanisms dyshomeostasis include activation L-type voltage-dependent transient potential ryanodine receptors, among many others. This review aims update calcium-dysregulation discuss targets molecules therapeutic based on their modulation.

Language: Английский

---

Endocannabinoid System: Chemical Characteristics and Biological Activity

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(2), P. 148 - 148

Published: Jan. 19, 2023

The endocannabinoid system (eCB) has been studied to identify the molecular structures present in Cannabis sativa. eCB consists of cannabinoid receptors, endogenous ligands, and associated enzymatic apparatus responsible for maintaining energy homeostasis cognitive processes. Several physiological effects cannabinoids are exerted through interactions with various such as CB1 CB2 vanilloid recently discovered G-protein-coupled receptors (GPR55, GPR3, GPR6, GPR12, GPR19). Anandamide (AEA) 2-arachidoylglycerol (2-AG), two small lipids derived from arachidonic acid, showed high-affinity binding both receptors. plays a critical role chronic pain mood disorders extensively because its wide therapeutic potential it is promising target development new drugs. Phytocannabinoids synthetic have shown varied affinities relevant treatment several neurological diseases. This review provides description components discusses how phytocannabinoids other exogenous compounds may regulate balance. Furthermore, we show hypo- or hyperfunctionality body related disorders, even integrative complementary health practices (ICHP) harmonizing eCB.

Language: Английский

---

Inhibiting degradation of 2-arachidonoylglycerol as a therapeutic strategy for neurodegenerative diseases

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 244, P. 108394 - 108394

Published: March 24, 2023

Endocannabinoids are endogenous lipid signaling mediators that participate in a variety of physiological and pathological processes. 2-Arachidonoylglycerol (2-AG) is the most abundant endocannabinoid full agonist G-protein-coupled cannabinoid receptors (CB1R CB2R), which targets Δ9-tetrahydrocannabinol (Δ9-THC), main psychoactive ingredient cannabis. While 2-AG has been well recognized as retrograde messenger modulating synaptic transmission plasticity at both inhibitory GABAergic excitatory glutamatergic synapses brain, growing evidence suggests also functions an terminator neuroinflammation response to harmful insults, thus maintaining brain homeostasis. Monoacylglycerol lipase (MAGL) key enzyme degrades brain. The immediate metabolite arachidonic acid (AA), precursor prostaglandins (PGs) leukotrienes. Several lines indicate pharmacological or genetic inactivation MAGL, boosts levels reduces its hydrolytic metabolites, resolves neuroinflammation, mitigates neuropathology, improves cognitive animal models neurodegenerative diseases, including Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's (PD), traumatic injury (TBI)-induced disease. Thus, it proposed MAGL potential therapeutic target for treatment diseases. As hydrolyzing 2-AG, several inhibitors have identified developed. However, our understanding mechanisms by produces neuroprotective effects diseases remains limited. A recent finding inhibition metabolism astrocytes, but not neurons, protects from TBI-induced neuropathology might shed some light on this unsolved issue. This review provides overview discusses possible underlying restraining degradation

Language: Английский

---

Extracellular vesicles released by microglia and macrophages carry endocannabinoids which foster oligodendrocyte differentiation

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 23, 2024

Introduction Microglia and macrophages can influence the evolution of myelin lesions through production extracellular vesicles (EVs). While microglial EVs promote in vitro differentiation oligodendrocyte precursor cells (OPCs), whether derived from aid or limit OPC maturation is unknown. Methods Immunofluorescence analysis for protein MBP was employed to evaluate impact primary rat on cultured differentiation. Raman spectroscopy liquid chromatography-mass spectrometry used define promyelinating lipid components obtained isolated human plasma. Results discussion Here we show that macrophage-derived do not differentiation, those released polarized towards an inflammatory state inhibit maturation. However, their cargo promotes a similar manner EVs. We identify endocannabinoids anandamide 2-arachidonoylglycerol by both microglia circulating Analysis presence endocannabinoid receptor antagonists SR141716A AM630 reveals key role vesicular From this study, EV-associated emerge as important mediators microglia/macrophage-oligodendrocyte crosstalk, which may be exploited enhance repair.

Language: Английский

---

The Administration of Cannabinoid Receptor 2 Agonist Decreases Binge-like Intake of Palatable Food in Mice

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1981 - 1981

Published: Feb. 25, 2025

Binge eating disorder (BED) is characterized by uncontrollable episodes of in a short period time, with subjective loss control overconsumption behavior. The role CB2 cannabinoid receptor (CB2R) plays binge-like intake has not yet been identified. In this regard, the present study aims to evaluate effect administration CB2R agonist, antagonist, or both on palatable food (PF) adolescent mice. We used 35 C57BL6/J male mice 30 postnatal days research; all animals were housed individually and had ad libitum access standard diet (SD) water. Animals evaluated for total 15 sessions Eating Test (BET), which consisted 1 h PF (chocolate sandwich cookies) according intermittent protocol, one-day access/one-day no-access. SD caloric intake, as well binge index (defined consuming ≥20% per day during PF), analyzed. Mice randomly assigned one following treatment groups: (1) control; (2) vehicle; (3) HU308, selective agonist; (4) AM630, antagonist; (5) AM630+HU308 coadministration antagonist agonists CB2R. All treatments administered intraperitoneally before BET sessions. Our results show that HU308 significantly reduced PF, while no significant differences found rest groups. These suggest activation decreases chronic conditions non-homeostatic feeding can be modulated Furthermore, may also modulate reward pathways, reducing behavior, could further explored future studies BED.

Language: Английский

---

Endocannabinoid signaling in brain diseases: Emerging relevance of glial cells

Glia, Journal Year: 2022, Volume and Issue: 71(1), P. 103 - 126

Published: March 30, 2022

The discovery of cannabinoid receptors as the primary molecular targets psychotropic Δ9 -tetrahydrocannabinol (Δ9 -THC) in late 1980s paved way for investigations on effects cannabis-based therapeutics brain pathology. Ever since, a wealth results obtained from studies human tissue samples and animal models have highlighted promising therapeutic potential cannabinoids endocannabinoids variety neurological disorders. However, clinical success has been limited major questions concerning endocannabinoid signaling need to be satisfactorily addressed, particularly with regard their role modulators glial cells neurodegenerative diseases. Indeed, recent brought into limelight diverse, often unexpected functions astrocytes, oligodendrocytes, microglia injury disease, thus providing scientific basis targeting treat This Review summarizes current knowledge cellular hallmarks its relevance chronic inflammatory

Language: Английский

---

Potential of CBD Acting on Cannabinoid Receptors CB1 and CB2 in Ischemic Stroke

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6708 - 6708

Published: June 18, 2024

Stroke is one of the leading causes death. It not only affects adult people but also many children. estimated that, every year, 15 million suffer a stroke worldwide. Among them, 5 die, while are left permanently disabled. In this sense, research to find new treatments should be accompanied with therapies combat neuronal death and avoid developing cognitive impairment dementia. Phytocannabinoids among compounds that have been used by mankind for longest period history. Their beneficial effects such as pain regulation or neuroprotection widely known make them possible therapeutic agents high potential. These bind cannabinoid receptors CB

Language: Английский

---

Unraveling the Hippocampal Molecular and Cellular Alterations behind Tramadol and Tapentadol Neurobehavioral Toxicity

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(6), P. 796 - 796

Published: June 17, 2024

Tramadol and tapentadol are chemically related opioids prescribed for the analgesia of moderate to severe pain. Although safer than classical opioids, they associated with neurotoxicity behavioral dysfunction, which arise as a concern, considering their central action growing misuse abuse. The hippocampal formation is known participate in memory learning processes has been documented contribute opioid dependence. Accordingly, present study assessed molecular cellular alterations Wistar rats intraperitoneally administered 50 mg/kg tramadol or eight alternate days. Alterations were found serum hydrogen peroxide, cysteine, homocysteine, dopamine concentrations upon exposure one both well 8-hydroxydeoxyguanosine gene expression levels panel neurotoxicity, neuroinflammation, neuromodulation biomarkers, through quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical analysis sections showed increased glial fibrillary acidic protein (GFAP) decreased cluster differentiation 11b (CD11b) expression, suggesting opioid-induced astrogliosis microgliosis. Collectively, results emphasize neuromodulator effects tapentadol, potential implications, underlining need prescribe use cautiously.

Language: Английский

---