Short-term high fat diet impairs memory, exacerbates the neuroimmune response, and evokes synaptic degradation via a complement-dependent mechanism in a mouse model of Alzheimer’s disease

Brain Behavior and Immunity, Год журнала: 2024, Номер 121, С. 56 - 69

Опубликована: Июль 21, 2024

Alzheimer's Disease (AD) is a neurodegenerative disease characterized by profound memory impairments, synaptic loss, neuroinflammation, and hallmark pathological markers. High-fat diet (HFD) consumption increases the risk of developing AD even after controlling for metabolic syndrome, pointing to role itself in increasing risk. In AD, complement system, an arm immune system which normally tags redundant or damaged synapses pruning, becomes pathologically overactivated leading tagging healthy synapses. While unhealthy link strong, underlying mechanisms are not well understood part due confounding variables associated with long-term HFD can independently influence brain. Therefore, we experimented short-term regimen isolate diet's impact on brain function without causing obesity. This project investigated effect 1) memory, 2) neuroinflammation including complement, 3) pathology markers, 4) 5) vitro microglial phagocytosis 3xTg-AD mouse model. Following either standard chow HFD, non-Tg mice were tested impairments. separate cohort mice, levels hippocampal inflammatory proteins, markers measured. For last set experiments, BV2 was evaluated. Synaptoneurosomes isolated from hippocampus fed incubated equal numbers microglia. The number microglia that phagocytosed synaptoneurosomes tracked over time live-cell imaging assay. Finally, receptor inhibitor (NIF) repeated Behavioral analysis showed had significantly impaired contextual cued fear compared further HFD. increased expression while decreasing marker only altering HFD-fed at higher rate than those chow-fed suggesting altered blocked this dose-dependent manner, demonstrating HFD-mediated increase dependent. study indicates over-activates cascade resulting poorer memory. data point as potential mechanistic culprit therapeutic target HFD's cognitive vulnerability AD.

Язык: Английский

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MEF2C Alleviates Postoperative Cognitive Dysfunction by Repressing Ferroptosis

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(10)

Опубликована: Сен. 30, 2024

Ferroptosis, a form of programmed cell death featured by lipid peroxidation, has been proposed as potential etiology for postoperative cognitive dysfunction (POCD). Myocyte-specific enhancer factor 2C (MEF2C), transcription expressed in various brain types, implicated disorders. This study sought to ascertain whether MEF2C governs capacity affecting ferroptosis.

Язык: Английский

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Lipid Dysregulation and Delirium in Older Adults: A Review of the Current Evidence and Future Directions

Brain Research Bulletin, Год журнала: 2025, Номер 224, С. 111299 - 111299

Опубликована: Март 12, 2025

Delirium is a complex medical condition marked by acute episodes of cognitive dysfunction and behavioral disturbances, with multifaceted etiology challenging management across various clinical settings. Older adults, particularly in postoperative contexts, are at increased risk developing delirium. Despite extensive research, single underlying pathophysiological mechanism for delirium remains elusive. However, emerging evidence suggests correlation between lipid dysregulation development elderly patients, especially This connection has led to proposed treatments targeting dyslipidemia associated neuroinflammatory effects acute-phase review aims synthesize current literature on the relationship older highlighting need further research into specific neurolipidome constituents age-related profile changes, potentially uncovering novel therapeutic strategies

Язык: Английский

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Intermittent fasting alleviates postoperative cognitive dysfunction by reducing neuroinflammation in aged mice

Brain Research Bulletin, Год журнала: 2024, Номер 216, С. 111034 - 111034

Опубликована: Июль 23, 2024

Elderly individuals undergoing surgical procedures are often confronted with the peril of experiencing postoperative cognitive dysfunction (POCD). Prior research has demonstrated exacerbating effect sevoflurane anesthesia on neuroinflammation, which can further deteriorate condition POCD in elderly patients. Intermittent fasting (IF) restricts food consumption to a specific time window and been ameliorate induced by neuropathic inflammation. We subjected 18-month-old male mice 16 hours 8 unrestricted eating over 24-hour period for 0, 1, 2, 4 weeks, followed abdominal exploration under anesthesia. In this study, we aim explore potential impact IF function aged surgery through preoperative implementation measures. The findings indicate two weeks leads significant enhancement learning memory capabilities following surgery. performance, as determined novel object recognition Morris water maze tests, well synaptic plasticity, measured vivo electrophysiological recordings, marked improvements. Furthermore, administration markedly enhances expression synaptic-associated proteins hippocampal neurons, concomitant decreasing pro-inflammatory factors reduced density microglial cells within brain region. To summarize, results study that may mitigate inflammation area brain. appears provide safeguard against impairment plasticity brought

Язык: Английский

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Dietary EPA and DHA enrichment of a high fat diet during doxorubicin-based chemotherapy attenuated neuroinflammatory gene expression in the brain of C57bl/6 ovariectomized mice

Brain Behavior and Immunity, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

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Dietary Supplementation with n-3 Polyunsaturated Fatty Acids Delays the Phenotypic Manifestation of Krabbe Disease and Partially Restores Lipid Mediator Production in the Brain—Study in a Mouse Model of the Disease

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(13), С. 7149 - 7149

Опубликована: Июнь 28, 2024

Lipid mediators from fatty acid oxidation have been shown to be associated with the severity of Krabbe disease (KD), a disorder linked mutations in galactosylceramidase (GALC) gene. This study aims investigate effects n-3 polyunsaturated (PUFA) supplementation on KD traits and metabolism using Twitcher (Tw) animals as natural model for KD. Wild-type (Wt), heterozygous (Ht), affected Tw were treated orally 36 mg PUFAs/kg body weight/day 10 35 days life. The end product PUFA peroxidation (8-isoprostane), lipid mediator involved resolution inflammatory exudates (resolvin D1), total amount PUFAs analyzed brains mice. In mice, delayed manifestation symptoms (p < 0.0001), bran, decreased 8-isoprostane amounts increased resolvin D1 levels 0.005) quantity 0.05). Furthermore, brain (r = -0.562, p 0.712, -0.690, 0.0001). For first time KD, are determine well production pro-resolving mediators. It is also that dietary leads slowing phenotypic presentation restoration production.

Язык: Английский

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Macaiba palm pulp (Acrocomia intumescens Drude) improves memory and induces anxiolytic-like behavior in dyslipidemic rats

Metabolic Brain Disease, Год журнала: 2024, Номер 40(1)

Опубликована: Дек. 13, 2024

Язык: Английский

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