Transcriptomics and biochemical evidence of trigonelline ameliorating learning and memory decline in the senescence-accelerated mouse prone 8 (SAMP8) model by suppressing proinflammatory cytokines and elevating neurotransmitter release

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

Published: Sept. 18, 2023

In recent years, exploring natural compounds with functional properties to ameliorate aging-associated cognitive decline has become a research priority ensure healthy aging. the present study, we investigated effects of Trigonelline (TG), plant alkaloid, on memory and spatial learning in 16-week-old senescence-accelerated mouse model SAMP8 using an integrated approach for molecular biology aspects. After 30 days oral administration TG at dose 5 mg/kg/day, mice were trained Morris Water Maze task. TG-treated exhibited significant improvement parameters escape latency, distance moved, annulus crossing index. Next, performed whole-genome transcriptome profiling hippocampus microarrays. Gene ontology analyses showed that wide range biological processes, including nervous system development, mitochondrial function, ATP synthesis, several signaling pathways related inflammation, autophagy, neurotransmitter release, significantly enriched compared nontreated. Further, nonlinear dimensionality reduction technique, Uniform Manifold Approximation Projection (UMAP), was applied identify clusters functions revealed primarily regulated followed by those involved release. addition, protein-protein interaction network analysis indicated may exert its through negatively modulating Traf6-mediated NF-κB activation. Finally, ELISA test treatment decreased proinflammatory cytokines- TNFα IL6 increased neurotransmitters- dopamine, noradrenaline, serotonin hippocampus. Altogether, our bio-cognitive highlights potential alleviating age-related impairment.

Language: Английский

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PM2.5 exposure exacerbates seizure symptoms and cognitive dysfunction by disrupting iron metabolism and the Nrf2-mediated ferroptosis pathway

The Science of The Total Environment, Journal Year: 2023, Volume and Issue: 910, P. 168578 - 168578

Published: Nov. 18, 2023

Language: Английский

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Unveiling the role of histone deacetylases in neurological diseases: focus on epilepsy

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Nov. 19, 2024

Abstract Epilepsy remains a prevalent chronic neurological disease that is featured by aberrant, recurrent and hypersynchronous discharge of neurons poses great challenge to healthcare systems. Although several therapeutic interventions are successfully utilized for treating epilepsy, they can merely provide symptom relief but cannot exert disease-modifying effect. Therefore, it urgent need explore other potential mechanism develop novel approach delay the epileptic progression. Since approximately 30 years ago, histone deacetylases (HDACs), versatile epigenetic regulators responsible gene transcription via binding histones or non-histone substrates, have grabbed considerable attention in drug discovery. There also substantial evidences supporting aberrant expressions and/activities HDAC isoforms reported epilepsy inhibitors (HDACi) been purposes this condition. However, specific mechanisms underlying role HDACs progression not fully understood. Herein, we reviewed basic information HDACs, summarized recent findings associated with roles diverse subunits discussed regulatory which affected development epilepsy. Additionally, provided brief discussion on as promising targets treatment, serving valuable reference study clinical translation field.

Language: Английский

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Oridonin exerts anticonvulsant profile and neuroprotective activity in epileptic mice by inhibiting NLRP3-mediated pyroptosis

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 134, P. 112247 - 112247

Published: May 16, 2024

Epilepsy is a chronic disabling disease poorly controlled by available antiseizure medications. Oridonin, bioactive alkaloid with anti-inflammatory properties and neuroprotective effects, can inhibit the increased excitability of neurons caused glutamate accumulation at cellular level. However, whether oridonin affects neuronal it has antiepileptic potential not been reported in animal models or clinical studies. Pentylenetetrazol was injected into mice to create model epilepsy. Seizure severity assessed using Racine scale, duration latency seizures were observed. Abnormal discharge detected electroencephalography, calcium imaging. Damage hippocampal evaluated Hematoxylin-Eosin Nissl staining. The expression NOD-like receptor thermal protein domain associated 3 (NLRP3) inflammasome other pyroptosis-related proteins determined western blotting immunofluorescence. A pyroptosis established supernatant BV2 cells treated lipopolysaccharide adenosine triphosphate stimulate neurons. Oridonin (1 5 mg/kg) reduced damage, seizures, shortened fully kindled epilepsy mice. decreased abnormal during epileptic episodes suppressed excitability. In vitro experiments showed that alleviated HT22 exerts effects inhibiting through NLRP3/caspase-1 pathway It also reduces vitro, suggesting its as therapy for

Language: Английский

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Brain tumor related epilepsy: pathophysiological approaches and rational management of antiseizure medication

Neurological Research and Practice, Journal Year: 2022, Volume and Issue: 4(1)

Published: Sept. 5, 2022

Brain tumor related epilepsy (BTRE) is a common complication of cerebral tumors and its incidence highly dependent on the type tumor, ranging from 10-15% in brain metastases to > 80% low grade gliomas. Clinical management challenging has take into account aspects beyond treatment non-tumoral epilepsy.Increasing knowledge about pathophysiology BTRE, particularly glutamatergic mechanisms oncogenesis epileptogenesis, might influence anti-tumor BTRE future. The first seizure implies diagnosis patients with tumors. Due lack prospective randomized trials general recommendations for focal epilepsies currently apply concerning initiation antiseizure medication (ASM). Non-enzyme inducing ASM preferable. Prospective are needed evaluate, if AMPA inhibitors like perampanel possess effects. withdrawal be weighed very carefully against risk recurrence, but can achievable selected patients. Permission drive possible some under well-defined conditions, requires thorough neurological, radiological, ophthalmological neuropsychological examination.An evolving future therapy. Randomized reliable endpoints needed. Management ASMs permission demands diagnostic as well neurooncological epileptological expertise.

Language: Английский

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The Neurovascular Unit Dysfunction in the Molecular Mechanisms of Epileptogenesis and Targeted Therapy

Neuroscience Bulletin, Journal Year: 2024, Volume and Issue: 40(5), P. 621 - 634

Published: March 30, 2024

Epilepsy is a multifaceted neurological syndrome characterized by recurrent, spontaneous, and synchronous seizures. The pathogenesis of epilepsy, known as epileptogenesis, involves intricate changes in neurons, neuroglia, endothelium, leading to structural functional disorders within neurovascular units culminating the development spontaneous epilepsy. Although current research on epilepsy treatments primarily centers around anti-seizure drugs, it imperative seek effective interventions capable disrupting epileptogenesis. To this end, comprehensive exploration molecular mechanisms underlying epileptogenesis holds promise identifying vital biomarkers for accurate diagnosis potential therapeutic targets. Emphasizing early timely intervention paramount, stands significantly improve patient prognosis alleviate socioeconomic burden. In review, we highlight unit provide theoretical basis drug

Language: Английский

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Anakinra Promotes M2 Microglia Activation during the Latent Phase of the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy

Journal of Evolutionary Biochemistry and Physiology, Journal Year: 2024, Volume and Issue: 60(2), P. 672 - 689

Published: March 1, 2024

Language: Английский

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An explanation of the role of pyroptosis playing in epilepsy

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 136, P. 112386 - 112386

Published: June 7, 2024

Language: Английский

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A Systematic Review of the Predictive and Diagnostic Uses of Neuroinflammation Biomarkers for Epileptogenesis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6488 - 6488

Published: June 12, 2024

A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the of inflammatory mediators epileptogenesis, its association with seizure severity, and correlation drug-resistant epilepsy (DRE). The study analysed articles published JCR journals from 2019 to 2024. search strategy comprised MESH, free terms “Neuroinflammation”, selective searches following single biomarkers that had previously selected relevant literature: “High mobility group box 1/HMGB1”, “Toll-Like-Receptor 4/TLR-4”, “Interleukin-1/IL-1”, “Interleukin-6/IL-6”, “Transforming growth factor beta/TGF-β”, “Tumour necrosis factor-alpha/TNF-α”. These queries were all combined MESH “Epileptogenesis” “Epilepsy”. We found 243 related neuroinflammation, 356 biomarker type. After eliminating duplicates, 324 evaluated, 272 excluded 55 evaluated authors. total 21 included qualitative evaluation, including 18 case–control studies, 2 case series, 1 prospective study. As conclusion, this provides acceptable support five biomarkers, TNF-α some soluble receptors (sTNFr2), HMGB1, TLR-4, CCL2 IL-33. Certain receptors, cytokines, chemokines are examples neuroinflammation-related may be crucial early diagnosis refractory or connected control epileptic seizures. Their value will better defined future studies.

Language: Английский

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The Gut-Brain Axis and Neuroinflammation in Traumatic Brain Injury

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 62(4), P. 4576 - 4590

Published: Oct. 28, 2024

Language: Английский

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