Estradiol metabolism by gut microbiota in women’s depression pathogenesis: inspiration from nature

Frontiers in Psychiatry, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 28, 2025

The recurrence and treatment resistance of depression remain significant issues, primarily due to an inadequate understanding its pathogenesis. Recent scientific evidence indicates that gut microbiota influence estradiol metabolism are associated with the development in nonpremenopausal women. Integrating existing studies on regulation by microorganisms nature relevance degradation products depression, recent explorations have further elucidated key mechanisms which catabolize through specific metabolic pathways. These emerging findings suggest unique effects may be one central drivers onset course non-menopausal

Language: Английский

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(R)-Ketamine attenuates LPS-induced endotoxin-derived delirium through inhibition of neuroinflammation

Psychopharmacology, Journal Year: 2021, Volume and Issue: 238(10), P. 2743 - 2753

Published: July 27, 2021

Language: Английский

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Toll-like receptors and NLRP3 inflammasome-dependent pathways in Parkinson’s disease: mechanisms and therapeutic implications

Journal of Neurology, Journal Year: 2022, Volume and Issue: 270(3), P. 1346 - 1360

Published: Dec. 3, 2022

Abstract Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder characterized by motor and non-motor disturbances as result of complex not fully understood pathogenesis, probably including neuroinflammation, oxidative stress, formation alpha-synuclein (α-syn) aggregates. As age the main risk factor for several disorders PD, aging immune system leading to inflammaging immunosenescence may contribute neuroinflammation PD onset progression; abnormal α-syn aggregation in context dysfunction favor activation nucleotide-binding oligomerization domain-like receptor (NOD) family pyrin domain containing 3 (NLRP3) inflammasome within microglial cells through interaction with toll-like receptors (TLRs). This process would further lead Caspase (Cas)-1, increased production pro-inflammatory cytokines (PC), subsequent impairment mitochondria damage dopaminergic neurons. All these phenomena are mediated translocation nuclear kappa-B (NF-κB) enhanced reactive oxygen species (ROS). To date, drugs treat mainly aimed at relieving clinical symptoms there no disease-modifying options reverse or stop progression. review outlines role TLR/NLRP3/Cas-1 pathway PD-related dysfunction, also focusing on specific therapeutic that might be used since early stages counteract dysfunction.

Language: Английский

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Dysfunction of NRG1/ErbB4 Signaling in the Hippocampus Might Mediate Long-term Memory Decline After Systemic Inflammation

Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 60(6), P. 3210 - 3226

Published: Feb. 25, 2023

Language: Английский

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Alzheimer’s genes in microglia: a risk worth investigating

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: Nov. 20, 2023

Abstract Despite expressing many key risk genes, the role of microglia in late-onset Alzheimer’s disease pathophysiology is somewhat ambiguous, with various phenotypes reported to be either harmful or protective. Herein, we review some findings from clinical and animal model investigations, discussing microglial genetics mediating perturbations homeostasis. We note that impairment protective may include prolonged insufficient activation, resulting dysregulated metabolomic (notably lipid-related) processes, compounded by age-related inflexibility dynamic responses. Insufficiencies mouse aggressive transgenic modelling imply severe limitations applying current methodologies for aetiological investigations. shortcomings, widely used amyloidosis tauopathy models have proven invaluable dissecting functional responses AD pathophysiology. Some recent advances brought tools closer human genetics, increasing validity both translational endeavours.

Language: Английский

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Effect of Acupuncture on the p38 Signaling Pathway in Several Nervous System Diseases: A Systematic Review

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(13), P. 4693 - 4693

Published: June 30, 2020

Acupuncture is clinically used to treat various diseases and exerts positive local systemic effects in several nervous system diseases. Advanced molecular clinical studies have continually attempted decipher the mechanisms underlying these of acupuncture. While a growing understanding pathophysiology shows it be related inflammation impair cell regeneration after ischemic events, relationship between therapeutic mechanism acupuncture p38 MAPK signal pathway has yet elucidated. This review discusses latest advancements identification effect on signaling We electronically searched databases including PubMed, Embase, Cochrane Library from their inception April 2020, using following keywords alone or combinations: “acupuncture”, “p38 pathway”, “signaling”, “stress response”, “inflammation”, “immune”, “pain”, “analgesic”, “cerebral injury”, “epilepsy”, “Alzheimer’s disease”, “Parkinson’s “dementia”, “degenerative”, “homeostasis”. Manual electroacupuncture confer by regulating proinflammatory cytokines, ion channels, scaffold proteins, transcription factors TRPV1/4, Nav, BDNF, NADMR1; consequently, regulates phenomena communication, remodeling, regeneration, gene expression. In this article, we found most common acupoints for relief disorders GV20, GV14, ST36, ST37, LI4. exhibits dual regulatory functions activating inhibiting different pathways, contributing an overall improvement symptoms function

Language: Английский

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Kai-Xin-San Inhibits Tau Pathology and Neuronal Apoptosis in Aged SAMP8 Mice

Molecular Neurobiology, Journal Year: 2022, Volume and Issue: 59(5), P. 3294 - 3309

Published: March 18, 2022

Alzheimer's disease (AD) is an age-related neurological disorder. Currently, there no effective cure for AD due to its complexity in pathogenesis. In light of the complex pathogenesis AD, traditional Chinese medicine (TCM) formula Kai-Xin-San (KXS), which was used amnesia treatment, has been proved improve cognitive function animal models. However, active ingredients and mechanism KXS have not yet clearly elucidated. this study, network pharmacology analysis predicts that yields 168 candidate compounds acting on 863 potential targets, 30 are associated with AD. Enrichment revealed therapeutic mechanisms inhibition Tau protein hyperphosphorylation, inflammation, apoptosis. Therefore, we chose 7-month-old senescence-accelerated mouse prone 8 (SAMP8) mice as model, harbors behavioral pathological hallmarks Subsequently, underlying action predicted by analyses were experimentally validated SAMP8 after intragastric administration 3 months. We observed upregulated AKT phosphorylation, suppressed GSK3β CDK5 activation, inhibited TLR4/MyD88/NF-κB signaling pathway attenuate hyperphosphorylation neuroinflammation, thus suppressing neuronal apoptosis improving impairment aged mice. Taken together, our findings reveal a multi-component multi-target attenuating progression contributing future development TCM modernization, including KXS, broader clinical application.

Language: Английский

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Steroid Sulfation in Neurodegenerative Diseases

Frontiers in Molecular Biosciences, Journal Year: 2022, Volume and Issue: 9

Published: Feb. 23, 2022

Steroid sulfation and desulfation participates in the regulation of steroid bioactivity, metabolism transport. The authors focused on balance three neurodegenerative diseases: Alzheimer´s disease (AD), Parkinson´s (PD), multiple sclerosis (MS). Circulating conjugates dominate their unconjugated counterparts, but steroids outweigh conjugated counterparts brain. Apart from neurosteroid synthesis central nervous system (CNS), most brain cross blood-brain barrier (BBB) periphery then may be further metabolized. Therefore, levels partly reflect situation CNS subsequently influence neuronal excitability have neuroprotective, neuroexcitatory, antidepressant memory enhancing effects. They also exert anti-inflammatory immunoprotective actions. Like steroids, sulfated ones modulate various ligand-gated ion channels. Conjugation by sulfotransferases increases water solubility facilitates sulfates, having greater half-lives than serve as a stock pool. Sulfotransferases are ubiquitous enzymes providing massive adrenal zona reticularis fasciculata. . sulfatase hydrolyzing is exceedingly expressed placenta low amounts including capillaries BBB which can rapidly hydrolyze sulfates coming across periphery. Lower dehydroepiandrosterone sulfate (DHEAS) plasma reduced sulfotransferase activity considered risk factors AD patients. shifted towards participate pathophysiology PD effects DHEAS counteract MS.

Language: Английский

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Novel lactoferrin-functionalized manganese-doped silica hollow mesoporous nanoparticles loaded with resveratrol for the treatment of ischemic stroke

Materials Today Advances, Journal Year: 2022, Volume and Issue: 15, P. 100262 - 100262

Published: June 2, 2022

Stroke is a central nervous system disease with high incidence at present. It can cause pathological changes such as oxidative stress, inflammation, neuronal apoptosis, and lead to disturbance of consciousness, disability, even death. Due the existence blood-brain barrier (BBB), most drugs cannot reach lesions exert their efficacy fully. Therefore, purpose this research was design lactoferrin functionalized hollow mesoporous manganese doped silica nanoparticles (LHMMSN) for delivery insoluble drug resveratrol (RES). The could help pass through BBB target inflammatory sites antioxidant anti-inflammatory neuroprotective effects. RES adsorbed into LHMMSN particle size about 140 nm by adsorption method, loading reached 39.32 ± 2.46%. In vitro in vivo experiments showed that LHMMSN-RES increase activity superoxide dismutase (SOD) glutathione peroxidase (GSH-Px), reduce brain reactive oxygen species (ROS) malondialdehyde (MDA) content, expression factors (IL-10) anti-apoptotic (bcl-2) tissue, tissue pro-inflammatory (TNF-α, IL-1β, IL-6) pro-apoptotic (BAX, Cleaved caspase-3) expression. summary, inflammation protect nerve cells inhibiting thereby promoting recovery motor function middle cerebral artery occlusion (MCAO) model rats.

Language: Английский

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Neuroprotective Effect of Methanolic Ajwa Seed Extract on Lipopolysaccharide-Induced Memory Dysfunction and Neuroinflammation: In Vivo, Molecular Docking and Dynamics Studies

Plants, Journal Year: 2023, Volume and Issue: 12(4), P. 934 - 934

Published: Feb. 18, 2023

Islamic literature has indicated that daily consumption of Ajwa dates heals a variety chronic diseases and disorders. The current research investigates the neuroprotective effect methanolic seed extract (MASE) on lipopolysaccharide (LPS)-induced cognitive deficits using multiple approaches. For animal studies, MASE (200 400 mg/kg, p.o.) was administrated for thirty consecutive days, four doses LPS (250 µg/kg, i.p.) were injected to induce neurotoxicity. Memory functions evaluated elevated plus-maze novel object recognition tests. Acetylcholine (ACh) neuroinflammatory markers (cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, transforming growth (TGF)-β1) estimated in brain tissues. Studies molecular docking dynamics conducted provide insight into molecular-level mechanisms. administration resulted significant reversal LPS-induced memory impairment both maze models. Both ACh levels an LPS-treated rat brain. In addition, lowered COX-2 proinflammatory cytokines (TNF-α IL-6) while increasing anti-inflammatory (IL-10 TGF-β1) Molecular modeling results revealed compound's ellagic acid, epicatechin, catechin, kaempferol, quercetin, apigenin have potential act as dual inhibitor acetylcholinesterase (AChE) can be responsible improvement cholinergic inflammatory conditions, cinnamic hesperidin, hesperetin, narengin, rutin compounds are only transmission. above acted by interacting with key residues Trp84, Asp72, Gly118, Ser200, Tyr334, His440, which hydrolysis AChE, is inhibited (Val349, Leu352, Tyr355, Tyr385, Ala527, Ser530, Leu531) hydrophobic channel. By promoting activity protecting neuroinflammation brain, provides neuroprotection against deficits. Our preliminary findings will help further drug discovery processes related neuroinflammation-related neurodegeneration.

Language: Английский

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