The Implications of Microglial Regulation in Neuroplasticity-Dependent Stroke Recovery

Biomolecules, Год журнала: 2023, Номер 13(3), С. 571 - 571

Опубликована: Март 21, 2023

Stroke causes varying degrees of neurological deficits, leading to corresponding dysfunctions. There are different therapeutic principles for each stage pathological development. Neuroprotection is the main treatment in acute phase, and functional recovery becomes primary subacute chronic phases. Neuroplasticity considered basis restoration rehabilitation after stroke, including remodeling dendrites dendritic spines, axonal sprouting, myelin regeneration, synapse shaping, neurogenesis. Spatiotemporal development affects spontaneous rewiring neural circuits brain networks. Microglia resident immune cells that contribute homeostasis under physiological conditions. activated immediately phenotypic polarization changes phagocytic function crucial regulating focal global inflammation recovery. We have previously shown neuroplasticity spatiotemporally consistent with microglial activation, suggesting microglia may a profound impact on stroke be key target post-stroke rehabilitation. In this review, we explore as well functions mechanisms polarization, phagocytosis. This followed by summary microglia-targeted rehabilitative interventions influence promote

Язык: Английский

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Sleep, Glial Function, and the Endocannabinoid System: Implications for Neuroinflammation and Sleep Disorders

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(6), С. 3160 - 3160

Опубликована: Март 9, 2024

The relationship between sleep, glial cells, and the endocannabinoid system represents a multifaceted regulatory network with profound implications for neuroinflammation cognitive function. molecular underpinnings of sleep modulation by its influence on cell activity are discussed, shedding light reciprocal relationships that govern these processes. Emphasis is placed understanding role cells in mediating neuroinflammatory responses their patterns. Additionally, this review examines how interfaces glia-immune signaling to regulate inflammatory cascades within central nervous system. Notably, consequences disrupted neuroinflammation, dysfunction addressed, encompassing neurodegenerative disorders, mood disturbances, decline. Insights into bidirectional function context explored, providing comprehensive perspective potential mechanisms underlying impairments associated disturbances. Furthermore, therapeutic avenues targeting mitigate restore homeostasis, normalize identification novel targets intricate holds promise addressing conditions characterized dysfunction. This work aims examine complexities neural regulation identify intervention.

Язык: Английский

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Potential Therapeutic Targets to Modulate the Endocannabinoid System in Alzheimer’s Disease

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(7), С. 4050 - 4050

Опубликована: Апрель 5, 2024

Alzheimer's disease (AD), the most common neurodegenerative (NDD), is characterized by chronic neuronal cell death through progressive loss of cognitive function. Amyloid beta (Aβ) deposition, neuroinflammation, oxidative stress, and hyperphosphorylated tau proteins are considered hallmarks AD pathology. Different therapeutic approaches approved Food Drug Administration can only target a single altered pathway instead various mechanisms that involved in pathology, resulting limited symptomatic relief almost no effect slowing down progression. Growing evidence on modulating components endocannabinoid system (ECS) proclaimed their neuroprotective effects reducing neurochemical alterations preventing cellular dysfunction. Recent studies mouse models have reported inhibitors fatty acid amide hydrolase (FAAH) monoacylglycerol (MAGL), hydrolytic enzymes for N-arachidonoyl ethanolamine (AEA) 2-arachidonoylglycerol (2-AG), respectively, might be promising candidates as therapeutical intervention. The FAAH MAGL alone or combination seem to produce neuroprotection reversing deficits along with Aβ-induced responses, death, delaying Their exact signaling need elucidated understanding brain intrinsic repair mechanism. aim this review was shed light physiology pathophysiology summarize experimental data roles inhibitors. In review, we also included CB1R CB2R modulators diverse modulate ECS mediated responses such anti-nociceptive, anxiolytic, anti-inflammatory actions AD. Future research would provide directions molecular development new interventions treatment

Язык: Английский

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Cannabinoid receptor 2 is necessary to induce toll‐like receptor‐mediated microglial activation

Glia, Год журнала: 2021, Номер 70(1), С. 71 - 88

Опубликована: Сен. 9, 2021

The tight regulation of microglia activity is key for precise responses to potential threats, while uncontrolled and exacerbated microglial neurotoxic. Microglial toll-like receptors (TLRs) are indispensable sensing different types assaults triggering an innate immune response. Cannabinoid receptor 2 (CB2) signaling a pathway control homeostasis activation, its activation connected changes in activity. We aimed investigate how CB2 impacts TLR-mediated activation. Here, we demonstrate that deletion causes dampened transcriptional response prototypic TLR ligands microglia. Loss results distinct gene expression profiles, morphology, show the CB2-mediated attenuation TLR-induced mainly p38 MAPK-dependent. Taken together, necessary fine-tune programs

Язык: Английский

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Endocannabinoid signaling in microglia

Glia, Год журнала: 2022, Номер 71(1), С. 71 - 90

Опубликована: Окт. 12, 2022

Abstract Microglia, the innate immune cells of central nervous system (CNS), execute their sentinel, housekeeping and defense functions through a panoply genes, receptors released cytokines, chemokines neurotrophic factors. Moreover, microglia are closely linked to constant communication with other cell types, among them neurons. Depending on signaling pathway type stimuli involved, outcome operation can be neuroprotective or neurodegenerative. Accordingly, increasingly becoming considered cellular targets for therapeutic intervention. Among signals controlling activity, endocannabinoid (EC) has been shown exert role in many neurological diseases. Like neurons, express functional EC produce degrade ECs. Interestingly, boosting leads an anti‐inflammatory phenotype. Nonetheless, little evidence is available microglia‐mediated effects compounds. This review focuses acting CNS physiological pathological conditions, namely CB1R, CB2R TRPV1‐mediated regulation properties. It also provides new evidence, which strengthens understanding mechanisms underlying control by Given broad expression glial neuronal cells, resulting picture need vivo studies transgenic mouse models dissect contribution EC‐derived

Язык: Английский

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Synthetic cannabinoids reduce the inflammatory activity of microglia and subsequently improve neuronal survival in vitro

Brain Behavior and Immunity, Год журнала: 2022, Номер 105, С. 29 - 43

Опубликована: Июнь 25, 2022

Язык: Английский

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Microglial Cannabinoid CB2 Receptors in Pain Modulation

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2348 - 2348

Опубликована: Янв. 25, 2023

Pain, especially chronic pain, can strongly affect patients' quality of life. Cannabinoids ponhave been reported to produce potent analgesic effects in different preclinical pain models, where they primarily function as agonists Gi/o protein-coupled cannabinoid CB1 and CB2 receptors. The receptors are abundantly expressed both the peripheral central nervous systems. activation is associated with psychotropic adverse effects, thus largely limiting its therapeutic potential. However, promising targets for treatment without immune cells. Additionally, resident cells system, microglia increasingly recognized critical players pain. Accumulating evidence has demonstrated that expression significantly increased activated spinal cord, which exerts protective consequences within surrounding neural circuitry by regulating activity microglia. In this review, we focused on recent advances understanding role microglial nociceptive circuitry, highlighting mechanism modulating implications receptor- selective agonist-mediated analgesia.

Язык: Английский

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Investigation of Cannabis sativa Phytochemicals as Anti-Alzheimer’s Agents: An In Silico Study

Plants, Год журнала: 2023, Номер 12(3), С. 510 - 510

Опубликована: Янв. 22, 2023

Cannabis sativa is a medicinal plant that has been known for years and used as an Ayurvedic medicine. This great potential in treating various types of brain diseases. Phytochemicals present this act antioxidants by maintaining synaptic plasticity preventing neuronal loss. Cannabidiol (CBD) Tetrahydrocannabinol (THC) are both beneficial Alzheimer’s disease increasing the solubility Aβ42 amyloid Tau aggregation. Apart from these therapeutic effects, there certain unknown functions phytochemicals we want to elucidate through study. In research, our approach analyze effect on multiple culprit enzymes disease, such AChE (Acetylcholinesterase), BChE (Butyrylcholinesterase), γ-secretase, BACE-1. study, compounds were selected Lipinski’s rule, ADMET, ProTox based toxicity. Molecular docking between (THCV, Cannabinol C2, Cannabidiorcol) mentioned above was obtained software programs including AutoDock Vina 4.2, AutoDock, iGEMDOCK. comparison Donepezil (BA = −8.4 kcal/mol, Ki 1.46 mM), Rivastigmine −7.0 0.02 Galantamine −7.1, 2.1 Cannabidiorcol −9.4 4.61 mM) shows significant inhibition AChE. On other hand, C2 −9.2 4.32 significantly inhibits Butyrylcholinesterase (BuChE) Memantine −6.8 0.54 mM). study sheds new light opens avenues elucidating role bioactive disease.

Язык: Английский

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Type 2 cannabinoid receptor expression on microglial cells regulates neuroinflammation during graft-versus-host disease

Journal of Clinical Investigation, Год журнала: 2024, Номер 134(11)

Опубликована: Апрель 25, 2024

Neuroinflammation is a recognized complication of immunotherapeutic approaches such as immune checkpoint inhibitor treatment, chimeric antigen receptor therapy, and graft versus host disease (GVHD) occurring after allogeneic hematopoietic stem cell transplantation. While T cells inflammatory cytokines play role in this process, the precise interplay between adaptive innate arms system that propagates inflammation central nervous remains incompletely understood. Using murine model GVHD, we demonstrate type 2 cannabinoid (CB2R) signaling plays critical pathophysiology neuroinflammation. In these studies, identify CB2R expression on microglial induces an activated phenotype which potentiates accumulation donor-derived proinflammatory cells, regulates chemokine gene regulatory networks, promotes neuronal death. Pharmacological targeting with brain penetrant inverse agonist/antagonist selectively reduces neuroinflammation without deleteriously affecting systemic GVHD severity. Thus, findings delineate therapeutically targetable neuroinflammatory pathway has implications for attenuation neurotoxicity potentially other cell-based approaches.

Язык: Английский

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A Proteomic Approach Identified TFEB as a Key Player in the Protective Action of Novel CB2R Bitopic Ligand FD22a against the Deleterious Effects Induced by β-Amyloid in Glial Cells

Cells, Год журнала: 2024, Номер 13(10), С. 875 - 875

Опубликована: Май 19, 2024

Neurodegenerative diseases (NDDs) are progressive multifactorial disorders of the nervous system sharing common pathogenic features, including intracellular misfolded protein aggregation, mitochondrial deficit, and inflammation. Taking into consideration multifaceted nature NDDs, development multitarget-directed ligands (MTDLs) has evolved as an attractive therapeutic strategy. Compounds that target cannabinoid receptor type II (CB2R) rapidly emerging novel effective MTDLs against such Alzheimer's disease (AD). We recently developed first CB2R bitopic/dualsteric ligand, namely FD22a, which revealed ability to induce neuroprotection with fewer side effects. To explore potential FD22a a multitarget drug for treatment we investigated here its prevent toxic effect β-amyloid (Aβ

Язык: Английский

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