Role of astrocytic mu-opioid receptors of the ventrolateral periaqueductal gray in modulating anxiety-like responses

Published: May 5, 2025

Background Mu-opioid receptors (MORs) are critical regulators mediating the modulation of several behavioral reactions, including analgesia, addiction, and sedation. Recent studies have reported that MORs closely associated with mood disorders or anxiety behaviors; however, underlying neural mechanisms remain unclear. The periaqueductal gray (PAG), a key brain area, participates in aversive emotional behaviors. show high expression ventrolateral PAG (vlPAG) region. This study explored preliminary role expressed vlPAG modulating Results Bilateral administration DAMGO, an MOR-specific agonist, into male mice elicited anxiety-like behaviors elevated plus maze tests. phenotype was reversed by conditional knockdown astrocytic MORs. In contrast, glutamatergic GABAergic were not involved MOR-dependent By using in vitro calcium imaging astrocytes chemical genetic technologies, we found can promote signaling, which efficiently induce Accordingly, interference signaling viral infection vlPAG-dependent Conclusion Our findings demonstrated astrocytic, but GABAergic, these effects accomplished MOR-elicited mechanisms. present provides theoretical basis for treating dysfunctions during MOR-targeted management.

Language: Английский

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Chemogenetic modulation in stroke recovery: A promising stroke therapy Approach

Brain stimulation, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Stroke remains a leading cause of long-term disability and mortality worldwide, necessitating novel therapeutic strategies to enhance recovery. Traditional rehabilitation approaches, including physical therapy pharmacological interventions, often provide limited functional improvement. Neuromodulation has emerged as promising strategy promote post-stroke recovery by enhancing neuroplasticity reorganization. Among various neuromodulatory techniques, chemogenetics, particularly Designer Receptors Exclusively Activated Drugs (DREADDs), offers precise, cell-type-specific, temporally controlled modulation neuronal glial activity. This review explores the mechanisms potential chemogenetic in stroke Preclinical studies have demonstrated that activation excitatory DREADDs (hM3Dq) neurons located within peri-infarct area or contralateral M1 been shown neuroplasticity, facilitate axonal sprouting, lead improved behavioral following stroke. Conversely, stimulation inhibitory (hM4Di) suppresses stroke-induced excitotoxicity, mitigates spreading depolarizations (PIDs), modulates neuroinflammatory responses. By targeting specific populations, chemogenetics enables phase-specific interventions-early inhibition minimize damage during acute phase late excitation plasticity phase. Despite its advantages over traditional neuromodulation such optogenetics deep brain stimulation, several challenges remain before can be translated into clinical applications. These include optimizing viral vector delivery, improving ligand specificity, minimizing off-target effects, ensuring receptor stability. Furthermore, integrating with existing strategies, brain-computer interfaces therapy, may facilitating adaptive neuroplasticity. Future research should focus on refining tools enable application. offering highly selective, reversible, minimally invasive approach, holds great for revolutionizing advancing personalized strategies.

Language: Английский

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The Role of Glial Cells in Different Phases of Migraine: Lessons from Preclinical Studies

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12553 - 12553

Published: Aug. 8, 2023

Migraine is a complex and debilitating neurological disease that affects 15% of the population worldwide. It defined by presence recurrent severe attacks disabling headache accompanied other symptoms. Important advancements have linked trigeminovascular system neuropeptide calcitonin gene-related peptide to migraine pathophysiology, but mechanisms underlying its pathogenesis chronification remain unknown. Glial cells are essential for correct development functioning nervous and, due implication in diseases, been hypothesised role migraine. Here we provide narrative review glia different phases through analysis preclinical studies. Current evidence shows astrocytes microglia involved initiation propagation cortical spreading depolarization, neurophysiological correlate aura. Furthermore, satellite glial within trigeminal ganglia implicated maintenance orofacial pain, suggesting phase Moreover, trigeminocervical central sensitization, chronic Taken altogether, emerged as key players future therapeutic strategies could be focused on targeting them reduce burden

Language: Английский

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Chemogenetic activation of microglial Gi signaling decreases microglial surveillance and impairs neuronal synchronization

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 12, 2024

Abstract Microglia actively survey the brain and dynamically interact with neurons to maintain homeostasis. Microglial Gi-protein coupled receptors (Gi-GPCRs) play a critical role in microglia-neuron communications. However, impact of temporally activating microglial Gi signaling on dynamics neuronal activity homeostatic remains largely unknown. In this study, we employed Gi-based Designer Receptors Exclusively Activated by Drugs (Gi-DREADD) selectively modulate pathway. By integrating chemogenetic approach vivo two-photon imaging, observed that exogenous activation transiently inhibited process dynamics, reduced activity, impaired synchronization. These altered functions were associated decrease interactions between microglia neuron somata. Altogether, study demonstrates acute, can regulate circuit function, offering potential pharmacological target for neuromodulation through microglia.

Language: Английский

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Neuroinflammation in the paraventricular nucleus of the hypothalamus precipitates visceral pain induced by pancreatic cancer in mice

Journal of Gastrointestinal Oncology, Journal Year: 2024, Volume and Issue: 15(1), P. 468 - 477

Published: Feb. 1, 2024

Ning-Ning Ji, Zhi-Yan Li, Shuang Cao, Bei Pei, Chen-Yu Jin, Yi-Fan Peng Mao, Hong Jiang, Bi-Fa Fan, Ming Xia

Language: Английский

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Application of optogenetic glial cells to neuron–glial communication

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Oct. 5, 2023

Optogenetic techniques combine optics and genetics to enable cell-specific targeting precise spatiotemporal control of excitable cells, they are increasingly being employed. One the most significant advantages optogenetic approach is that it allows for modulation nearby cells or circuits with millisecond precision, enabling researchers gain a better understanding complex nervous system. Furthermore, neuron activation permits regulation information processing in brain, including synaptic activity transmission, also promotes nerve structure development. However, optimal conditions remain unclear, further research required identify types can effectively precisely function. Recent studies have described glial manipulation coordinating reciprocal communication between neurons glia. Optogenetically stimulated modulate central system provide structural support fibers peripheral These advances promote effective use optogenetics, although experiments needed. This review describes critical role reviews applications several as well their significance neuron–glia interactions. Together, briefly discusses therapeutic potential feasibility optogenetics.

Language: Английский

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Chemogenetic activation of astrocytic Gi signaling promotes spinogenesis and motor functional recovery after stroke

Glia, Journal Year: 2024, Volume and Issue: 72(6), P. 1150 - 1164

Published: March 4, 2024

Abstract Ischemic stroke is the leading cause of adult disability. The rewiring surviving neurons fundamental process for functional recovery. Accumulating evidence implicates astrocytes in synapses and neural circuits formation, but few studies have further studied how to enhance effects on synapse after its impacts post‐stroke In this study, we made use chemogenetics specifically activate astrocytic Gi signaling peri‐infarcted sensorimotor cortex at different time epochs a mouse model photothrombotic stroke. We found that early activation hM4Di by CNO modulates astrocyte activity upregulates synaptogenic molecules including thrombospondin‐1 (TSP1) as revealed bulk RNA‐sequencing, no significant improvement was observed dendritic spine density behavioral performance grid walking test. Interestingly, when manipulation initiated subacute phase stroke, recovery motor function could be effectively promoted, accompanied increased TSP1 expression. Our data highlight important role remodeling during repair suggest potential strategy regeneration, circuit rewiring,

Language: Английский

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DREADD Microglia? Targeted Microglial Gi Activation in the Acute Phase can Reduce Seizure Severity, but is Detrimental in the Long Term

Epiliepsy currents/Epilepsy currents, Journal Year: 2024, Volume and Issue: 24(6), P. 420 - 422

Published: Sept. 28, 2024

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Language: Английский

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Fatty acid–binding protein 3 is involved in the increase in inflammatory cytokine levels during lipopolysaccharide–induced microglial activation and affects the pain behavior

PAIN RESEARCH, Journal Year: 2024, Volume and Issue: 39(1), P. 46 - 52

Published: Oct. 10, 2024

Fatty acid–binding protein 3 (FABP3) is involved in intracellular lipid transport to cytosolic organelles. It also performs unique physiological functions, acting as a diagnostic or predictive biomarker for various diseases. We previously reported that hypothalamic FABP3 levels are upregulated under pain and co–expressed microglia. However, the specific roles of microglia remain unknown. Therefore, this study, we aimed assess involvement lipopolysaccharide (LPS)–induced increase inflammatory cytokine determine its effects on mouse microglial MG6 cells postoperative model mice. were treated with LPS activate cytoplasmic fraction was collected sample after 24 hours. FABP–IN–1 used non–selective FABP inhibitor, small interfering RNA (siFABP3) knockdown. Changes expression each gene analyzed via real–time polymerase chain reaction. In cells, (100 1000 ng/mL) significantly increased tumor necrosis factor–α, interleukin–6, mRNA levels; however, siFABP3 suppressed effect. Furthermore, repeated intracerebroventricular injection behavior Overall, our results suggest partly induction activation, thereby affecting brain.

Language: Английский

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Practice of Peritoneal Adhesions in Osteopathic Medicine: Part 2

Cureus, Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 7, 2023

Peritoneal adhesions are an unwanted and frequent event following abdominal surgery, with a response rate that can reach 100%. The be symptomatic, becoming source of pain discomfort for the patient, or asymptomatic, possible chronic acute visceral dysfunction. article reviews what diagnostic strategies discusses could causes lead to in presence adhesions. text reports knowledge literature on manual treatment illustrates symptoms not easily recognized by clinician. To conclude, proposes osteopathic approaches derived from clinical experience has been explained about formation peritoneal Research must make further efforts identify only triggering neogenesis but also seek most appropriate non-invasive treatments help patient.

Language: Английский

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