Urolithin-A Derivative UAS03 Improves Cognitive Deficits and Memory by Activating Nrf2 Pathways to Alleviate Oxidative Stress and Neuroinflammation

ACS Chemical Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Апрель 14, 2025

Neuroinflammation is a key factor in age-related cognitive decline and memory impairment. UAS03, potent synthetic analogue of Urolithin-A, has demonstrated anti-inflammatory antioxidant properties. This investigation examined the neuroprotective effect UAS03 on lipopolysaccharide (LPS) induced neuroinflammation, its associated impairments, deficits, depression-like behaviors. Intracerebroventricular administration LPS (12 μg/kg) was performed to induce neuroinflammation mice, followed by 7 day treatment with at 10 30 mg/kg doses. Mice were evaluated for depressive anxiety-like behavior, spatial memory, learning functions using series neurobehavioral test paradigms. Histopathological molecular analyses conducted hematoxylin-eosin cresyl violet staining, immunohistochemistry, ELISA, Western blotting techniques. We have found that, significantly enhanced impaired while concurrently reducing symptoms. Furthermore, compound attenuated neuronal damage decreased expression IBA-1 GFAP hippocampal region. Through activation nuclear erythroid 2-related 2 (Nrf2) signaling pathway, effectively mitigated markers oxidative stress reduced levels pro-inflammatory factors, including IL-1β, TNF-α, COX-2. Cumulatively, this study provides compelling evidence that exerts effects regulating essential pathways involved mechanisms, suggesting potential as preventative measure against impairments neuroinflammation.

Язык: Английский

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Astrocytes Mediate Psychostimulant‐Induced Alterations of Spike‐Timing Dependent Synaptic Plasticity

Glia, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

ABSTRACT At cellular and circuit levels, drug addiction is considered a dysregulation of synaptic plasticity. In addition, dysfunction the glutamate transporter 1 (GLT‐1) in nucleus accumbens (NAc) has also been proposed as mechanism underlying addiction. However, impact GLT‐1 alterations NAc remain unclear. Here we show that 10 days withdraw after 5 treatment with cocaine or amphetamine decreases expression astrocytes, which results prolongation excitatory postsynaptic potential (EPSP) decay kinetics D1 receptor‐containing medium spiny neurons (D1R‐MSNs). Using spike timing dependent plasticity (STDP) paradigm, found enlargement EPSP duration switching LTP elicited control animals to LTD psychostimulant‐treated mice. contrast D1‐MSNs, D2‐MSNs did not display changes Notably, psychostimulant‐induced transmission effects were absent IP3R2 −/− mice, lack astrocyte calcium signal, but mimicked by selective astrocytes stimulation DREADDs. Finally, ceftriaxone, upregulates GLT‐1, restored normal function, kinetics, Therefore, propose increase dopaminergic levels NAc, stimulates downregulates GLT‐1. The decreased function prolonged leading modulation STDP, transforming observed into Present work reveals novel induced these drugs abuse.

Язык: Английский

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Astrocyte-Secreted Lcn2 Modulates Dendritic Spine Morphology

Cells, Год журнала: 2025, Номер 14(3), С. 159 - 159

Опубликована: Янв. 21, 2025

Learning and memory formation rely on synaptic plasticity, the process that changes strength in response to neuronal activity. In tripartite synapse concept, molecular signals affect morphology originate not only from pre- post-synaptic terminals but also astrocytic processes ensheathing many synapses. Despite significant progress made understanding contribution a few plasticity-related proteins have been identified so far. this study, we present evidence indicating role of astrocyte-secreted Lipocalin-2 (Lcn2) plasticity. We show Lcn2 expression is induced hippocampal astrocytes kainate-evoked aberrant plasticity model. Next, demonstrate chemically long-term potentiation (cLTP) similarly increases neuronal–glial co-cultures, glutamate causes immediate release these cultures. Additionally, through experiments primary cultures, reveal triggered by calcium signaling, brief treatment co-cultures with alters dendritic spines. Based findings, propose as an activity-dependent molecule released influences spine morphology.

Язык: Английский

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Regulation of Postoperative Cognitive Dysfunction by Glutathione Under Various Pathways: A Narrative Review

Journal of Biochemical and Molecular Toxicology, Год журнала: 2025, Номер 39(2)

Опубликована: Фев. 1, 2025

Postoperative cognitive dysfunction (POCD) is a common neurological complication after surgery and general anesthesia, the incidence increases with age. Will have negative impact on patients, family society. At present, neuroinflammation oxidative stress are main recognized mechanisms. Glutathione (GSH) powerful reducing agent may be related to POCD. Using medical search engines such as PubMed, Web of Science, we analyzed articles topics as: POCD, GSH, microglia, astrocyte, oligodendrocyte, ferroptosis, BDNF, Neuroinflammation, stress. The above searched in databases using Boolean operations. We included original articles, reviews other article types books. According reviewed literature, GSH treatment for Specific targeted therapies POCD still sparse, therefore, implementation preventive strategies appears remain optimal attitude. Further research needed better understanding

Язык: Английский

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Advances in Optogenetics and Thermogenetics for Control of Non-Neuronal Cells and Tissues in Biomedical Research

ACS Chemical Biology, Год журнала: 2025, Номер unknown

Опубликована: Март 8, 2025

Optogenetics and chemogenetics are relatively new biomedical technologies that emerged 20 years ago have been evolving rapidly since then. This has made possible by the combined use of genetic engineering, optics, electrophysiology. With development optogenetics thermogenetics, molecular tools for cellular control continuously being optimized, studied, modified, expanding both their applications uses. The most notable changes occurred in basic life sciences, especially neurobiology activation neurons to behavior. Currently, these methods gone far beyond used cardiovascular research, potential cancer therapy, metabolism, etc. In this review, we provide brief information on types optogenetic thermogenetic methods─microbial rhodopsins proteins TRP superfamily─and also consider field non-neuronal tissues mammalian cells. We prospects thermogenetics research.

Язык: Английский

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Advancing Alzheimer’s disease therapy through engineered exosomal Macromolecules

Brain Research, Год журнала: 2025, Номер unknown, С. 149590 - 149590

Опубликована: Март 1, 2025

Язык: Английский

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Neuroimmune signaling mediates astrocytic nucleocytoplasmic disruptions and stress granule formation associated with TDP-43 pathology

Neurobiology of Disease, Год журнала: 2025, Номер unknown, С. 106939 - 106939

Опубликована: Май 1, 2025

Alterations in transactivating response region DNA-binding protein 43 (TDP-43) are prevalent amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurological disorders. TDP-43 influences neuronal functions might also affect glial cells. However, specific intracellular effects of alterations on cells underlying mechanisms not clear. We report that dysregulation mouse human cortical astrocytes causes nucleoporin mislocalization, nuclear envelope remodeling, changes nucleocytoplasmic transport. These dependent interleukin-1 (IL-1) receptor activity factor kappa-light-chain-enhancer activated B (NF-κB) signaling associated with the formation cytoplasmic stress granules. Stimulation IL-1 receptors NF-κB necessary sufficient to induce astrocytic granules rapid changes, which broadly alleviated by inhibition integrated response. findings establish neuroimmune factors can through signaling, revealing mechanistic convergence proteinopathy pathways onto disruptions may occur diverse conditions.

Язык: Английский

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Chronic Chemogenetic Activation of Astrocytes in the Murine Mesopontine Region Leads to Disturbances in Circadian Activity and Movement

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(10), С. 4793 - 4793

Опубликована: Май 16, 2025

We have previously shown that neuromodulatory actions on astrocytes can elicit metabotropic glutamate- and N-methyl-D-aspartate receptor-dependent tonic changes in excitability the mesopontine region. Although vitro experiments explored robust effects, vivo significance of our findings remained unknown. In this project, chronic chemogenetic activation its movement, circadian activity, acoustic startle spatial memory were tested. The control group young adult male mice where expressed only mCherry fluorescent tag was compared to expressing hM3D(Gq) actuator. Chronic astrocyte reduced amplitude reflex increased locomotion speed resting period. Gait alterations also demonstrated but no change explored. As a potential background these findings, astrocytic decreased cholinergic neuronal number 54% non-cholinergic 76% control. conclusion, consequential decrease led disturbances movement activity resembling brainstem-related symptoms progressive supranuclear palsy, raising possibility overactivation is involved pathogenesis disease.

Язык: Английский

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Chemogenetic and optogenetic tools revolutionizing the study of astrocytes in memory

Current Opinion in Neurobiology, Год журнала: 2025, Номер 93, С. 103057 - 103057

Опубликована: Май 28, 2025

Memory research has been historically centered around neurons, but the understanding that neurons do not work alone is lately gaining traction. Investigation of astrocytes provides evidence involvement these glial cells throughout all memory stages and in many types tests. This field constantly developing changing through adoption a variety techniques. In this review, we will focus on recent papers have used optogenetic chemogenetic tools, which are time-restricted cell-type specific, to investigate astrocytic memory. We also discuss some new tools starting be implemented astrocyte how they may future exploration link between specific activity

Язык: Английский

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Alzheimer’s Disease, Obesity, and Type 2 Diabetes: Focus on Common Neuroglial Dysfunctions (Critical Review and New Data on Human Brain and Models)

Brain Sciences, Год журнала: 2024, Номер 14(11), С. 1101 - 1101

Опубликована: Окт. 30, 2024

Obesity, type 2 diabetes (T2D), and Alzheimer's disease (AD) are pathologies that affect millions of people worldwide. They have no effective therapy difficult to prevent control when they develop. It has been known for many years these diseases pathogenic aspects in common. We highlight this review neuroglial cells (astroglia, oligodendroglia, microglia) play a vital role the origin, clinical-pathological development, course brain neurodegeneration. Moreover, we include new results T2D-AD mouse model (APP+PS1 mice on high-calorie diet) investigating.

Язык: Английский

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