Caffeic Acid Phenethyl Ester Suppresses Oxidative Stress and Regulates M1/M2 Microglia Polarization via Sirt6/Nrf2 Pathway to Mitigate Cognitive Impairment in Aged Mice following Anesthesia and Surgery

Antioxidants, Год журнала: 2023, Номер 12(3), С. 714 - 714

Опубликована: Март 13, 2023

Postoperative cognitive dysfunction (POCD) is a severe neurological complication after anesthesia and surgery. However, there still lack of effective clinical pharmacotherapy due to its unclear pathogenesis. Caffeic acid phenethyl ester (CAPE), which obtained from honeybee propolis medicinal plants, shows powerful antioxidant, anti-inflammatory, immunomodulating properties. In this study, we aimed evaluate whether CAPE mitigated impairment following surgery potential underlying mechanisms in aged mice. Here, isoflurane tibial fracture were used as the POCD model, H2O2-induced BV2 cells established microglial oxidative stress model. We revealed that pretreatment suppressed promoted switch microglia M1 M2 type hippocampus, thereby ameliorating caused by Further investigation indicated upregulated hippocampal Sirt6/Nrf2 expression Moreover, mechanistic studies demonstrated potent effects on reducing ROS generation promoting protective polarization attenuated specific Sirt6 inhibitor, OSS_128167. summary, our findings opened promising avenue for prevention through enhanced pathway suppress well favor polarization.

Язык: Английский

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Melatonin Can Modulate Neurodegenerative Diseases by Regulating Endoplasmic Reticulum Stress

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2381 - 2381

Опубликована: Янв. 25, 2023

As people age, their risks of developing degenerative diseases such as cancer, diabetes, Parkinson’s Disease (PD), Alzheimer’s (AD), rheumatoid arthritis, and osteoporosis are generally increasing. Millions worldwide suffer from these they age. In most countries, neurodegenerative recognized the number one cause afflicting elderly. Endoplasmic reticulum (ER) stress has been suggested to be associated with some human neurological diseases, PD AD. Melatonin, a neuroendocrine hormone mainly synthesized in pineal gland, is involved pleiotropically biological functions, including control circadian rhythm, immune enhancement, antioxidant, anti-aging, anti-tumor effects. Although there many papers on prevention or suppression by melatonin, very few about effects melatonin ER neurons diseases. This paper aims summarize present reported so far, focusing its related stress. Studies have shown that primary target molecule for CHOP, PERK GRP78/BiP secondary molecules. Therefore, crucial protecting treating neurodegeneration against

Язык: Английский

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Impaired synaptic plasticity and decreased glutamatergic neuron excitability induced by SIRT1/BDNF downregulation in the hippocampal CA1 region are involved in postoperative cognitive dysfunction

Cellular & Molecular Biology Letters, Год журнала: 2024, Номер 29(1)

Опубликована: Май 23, 2024

Abstract Background Postoperative cognitive dysfunction (POCD) is a common complication after anesthesia/surgery, especially among elderly patients, and poses significant threat to their postoperative quality of life overall well-being. While it widely accepted that patients may experience POCD following the exact mechanism behind this phenomenon remains unclear. Several studies have indicated interaction between silent mating type information regulation 2 homologue 1 (SIRT1) brain-derived neurotrophic factor (BDNF) crucial in controlling function strongly linked neurodegenerative disorders. Hence, research aims explore how SIRT1/BDNF impacts decline caused by anesthesia/surgery aged mice. Methods Open field test (OFT) was used determine whether affected motor ability mice, while 18 months old mice evaluated with Novel object recognition (NORT), Object location (OLT) Fear condition (FC). The expressions SIRT1 other molecules were analyzed western blot immunofluorescence staining. hippocampal synaptic plasticity detected Golgi staining Long-term potentiation (LTP). effects BDNF overexpression as well chemogenetic activation glutamatergic neurons CA1 region vesicular glutamate transporter (VGLUT1) on further investigated. Results results revealed older exhibited impairment intramedullary fixation tibial fracture. Additionally, notable decrease expression neuronal excitability observed. By increasing levels or enhancing neuron region, possible effectively mitigate ameliorate dysfunction. Conclusions leading changes could be contributing anesthesia/surgery. Graphical

Язык: Английский

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Alleviating CB2-Dependent ER Stress and Mitochondrial Dysfunction Improves Chronic Cerebral Hypoperfusion-Induced Cognitive Impairment

Journal of Neuroimmune Pharmacology, Год журнала: 2024, Номер 19(1)

Опубликована: Янв. 12, 2024

Abstract Augmentation of endoplasmic reticulum (ER) stress may trigger excessive oxidative stress, which induces mitochondrial dysfunction. The fatty acid amide hydrolase inhibitor, URB597, shows anti-oxidation characteristics in multiple neurological disorders. present study aimed to determine whether inhibition ER was involved the protective effects URB597 against chronic cerebral hypoperfusion (CCH)-induced cognitive impairment. Hippocampal HT-22 cells were exposed oxygen-glucose deprivation. cell viability, apoptosis, ATP, and levels assessed following treatment with benzenebutyric (4-PBA), thapsigargin (TG). Furthermore, on related pathways investigated CCH animal model, including Morris water maze testing cognition, western blotting analysis signaling, transmission electron microscopy ultrastructure changes. results suggested that ischemia caused upregulation signaling-related proteins, dysfunction, neuronal ultrastructural injuries mitochondria-associated membranes, decline. Co-immunoprecipitation experiments confirmed interaction between CB2 β-Arrestin1. Inhibiting by improved these changes activating CB2/β-Arrestin1 reversed antagonist, AM630. Together, identified a novel mechanism involving CCH-induced impairment alleviation CB2-dependent this as potential target for therapy ischemic cerebrovascular diseases. Graphical

Язык: Английский

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Exosomes Derived from M2 Microglial Cells Modulated by 1070‐nm Light Improve Cognition in an Alzheimer's Disease Mouse Model

Advanced Science, Год журнала: 2023, Номер 10(32)

Опубликована: Сен. 13, 2023

Abstract Near‐infrared photobiomodulation has been identified as a potential strategy for Alzheimer's disease (AD). However, the mechanisms underlying this therapeutic effect remain poorly characterize. Herein, it is illustrate that 1070‐nm light induces morphological alteration of microglia from an M1 to M2 phenotype secretes exosomes, which alleviates β‐amyloid burden improve cognitive function by ameliorating neuroinflammation and promoting neuronal dendritic spine plasticity. The results show 4 J cm −2 at 10‐Hz frequency prompts with inflammatory type switch anti‐inflammatory type. This secretion microglial‐derived exosomes containing miR‐7670‐3p, targets activating transcription factor 6 (ATF6) during endoplasmic reticulum (ER) stress. Moreover, found miR‐7670‐3p reduces ATF6 expression further ameliorate ER stress, thus attenuating response protecting integrity neurons in cortex hippocampus 5xFAD mice, ultimately leading improvements function. study highlights critical role derive light‐modulated treating AD may provide theoretical basis treatment use near‐infrared photobiomodulation.

Язык: Английский

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Microglial NOX2 as a therapeutic target in traumatic brain injury: Mechanisms, Consequences, and Potential for Neuroprotection

Ageing Research Reviews, Год журнала: 2025, Номер unknown, С. 102735 - 102735

Опубликована: Март 1, 2025

Язык: Английский

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Modulation of neural circuits by melatonin in neurodegenerative and neuropsychiatric disorders

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2024, Номер 397(6), С. 3867 - 3895

Опубликована: Янв. 16, 2024

Язык: Английский

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MicroRNA-124 negatively regulates STAT3 to alleviate hypoxic-ischemic brain damage by inhibiting oxidative stress

Aging, Год журнала: 2024, Номер unknown

Опубликована: Фев. 5, 2024

MicroRNA-124 (miR-124) is implicated in various neurological diseases; however, its significance hypoxic-ischaemic brain damage (HIBD) remains unclear. This study aimed to elucidate the underlying pathophysiological mechanisms of miR-124 HIBD. In our performed on oxygen-glucose deprivation followed by reperfusion (OGD)/R-induced primary cortical neurons, a substantial reduction was observed. Furthermore, upregulation significantly mitigated oxidative stress, apoptosis, and mitochondrial impairment. We demonstrated that interacts with signal transducer activator transcription 3 (STAT3) exert biological function using dual-luciferase reporter gene assay. As duration OGD increased, exhibited negative correlation STAT3. STAT3 overexpression notably attenuated protective effects mimics, while knockdown reversed adverse inhibitor. Subsequently, we conducted an HIBD model rats. vivo experiments, cerebral infarction volume, edema, improved recovery summary, neuroprotective miR-124/STAT3 axis were confirmed model. MiR-124 may serve as potential biomarker significant therapeutic implications for

Язык: Английский

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CRHR1 antagonist alleviated depression-like behavior by downregulating p62 in a rat model of post-stroke depression

Experimental Neurology, Год журнала: 2024, Номер 378, С. 114822 - 114822

Опубликована: Май 31, 2024

Язык: Английский

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Melatonin regulates endoplasmic reticulum stress in diverse pathophysiological contexts: A comprehensive mechanistic review

Journal of Cellular Physiology, Год журнала: 2024, Номер 239(11)

Опубликована: Июль 22, 2024

The endoplasmic reticulum (ER) is crucial for protein quality control, and disruptions in its function can lead to various diseases. ER stress triggers an adaptive response called the unfolded (UPR), which either restore cellular homeostasis or induce cell death. Melatonin, a safe multifunctional compound, shows promise controlling could be valuable therapeutic agent managing UPR. By regulating mitochondrial functions, melatonin helps maintain via reduction of oxidative stress, inflammation, apoptosis. Melatonin directly indirectly interfere with ER-associated sensors downstream targets UPR, impacting death, autophagy, molecular repair, among others. Crucially, this review explores mechanistic role on diseases including liver damage, neurodegeneration, reproductive disorders, pulmonary disease, cardiomyopathy, insulin resistance, renal dysfunction, cancer. Interestingly, while it alleviates burden most pathological contexts, paradoxically stimulate cancer cells, highlighting intricate involvement homeostasis. With numerous successful studies using vivo vitro models, continuation clinical trials imperative fully explore melatonin's potential these conditions.

Язык: Английский

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