LCN2 blockade mitigating metabolic dysregulation and redefining appetite control in type 2 diabetes

Metabolic Brain Disease, Journal Year: 2025, Volume and Issue: 40(1)

Published: Jan. 14, 2025

Abstract LCN2 has an osteokine important for appetite regulation; in type 2 diabetes (T2D) it is not known whether regulation mediated by the brain altered. In this work, we focus on exploring role of blocking metabolic health and within central nervous system mice with T2D. Material methods: 4-week-old male C57BL/6 were used, divided into four experimental groups: intact, T2D, TD2/anti-LCN2, T2D/IgG as isotype control. T2D was induced low doses streptozotocin a high-carbohydrate diet. blockade performed intraperitoneal administration polyclonal anti-LCN2 antibody. We analyzed parameters, food intake, feeding patterns, serum leptin concentrations. another group intact or mice, effect recombinant consumption fasting-refeeding test and, expression cFOS sections, specifically hypothalamus, piriform cortex, visceral area, arcuate nucleus caudate-putamen. Results: caused increase LCN2, without alterations Ad libitum feeding, but changes pattern associated LCN2-cFOS signalling hypothalamic non-hypothalamic regions. Blocking improved increased restored after fasting, which enhanced brain. Conclusions: restores normalizes normalizing different Graphical

Language: Английский

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Mechanism of LCN2 in cerebral ischemia-reperfusion injury

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: March 20, 2025

Cerebral ischemia-reperfusion injury (CIRI) is a complex pathophysiological process faced by brain tissues after ischemic stroke treatment, which involves mechanisms of inflammatory response, oxidative stress and apoptosis, severely affects treatment outcome. Lipocalin-2 (LCN2), an acute-phase protein, significantly up-regulated CIRI promotes neural repair enhancing astrocyte phagocytosis, but its over-activation may also trigger secondary inflammation demyelination injury. LCN2 plays key role in neuroinflammation regulation regulating the polarization state astrocytes release factors, affect integrity blood–brain barrier variety pathologic processes. In view important CIRI, this article reviews mechanism LCN2, aiming to provide new ideas methods for stroke.

Language: Английский

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Early stage of metabolic dysfunction associated steatotic liver disease disrupts circadian rhythm and induces neuroinflammation in rats

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 27, 2025

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a chronic liver disease affecting 25% of the European population, with rising global incidence. damage includes ballooning, steatosis, inflammation and fibrosis. Associated brain disorders include sleep, cognitive issues, anxiety, depression. While neurological complications in advanced MASLD are well documented, early cerebral manifestations remain largely unexplored. This study aimed at developing an rat model to assess onset damage, focusing on impairments circadian cycle rhythm associated neuroinflammation. Sprague Dawley rats were divided into two groups: one received high-fat, high-cholesterol (HFHC) diet for 90 days, while other standard diet. Histological analysis showed significant hepatic HFHC group (p < 0.01). These lesions correlated elevated triglycerides 0.01), increased Alanine Aminotransferase, Aspartate total cholesterol, low-density lipoprotein, alongside decreased plasma high-density lipoprotein. Behavioural using activity wheels revealed that steadily maintained their level during rest periods when compared controls 0.05). behavioural alteration occurred neuroinflammation, demonstrated by changes expression 36 17 inflammatory mediators cerebellum frontal cortex respectively. increase glial cell markers (Aif1 Gfap genes) number microglial cells, differently. shows disturbances, which could reflect sleep humans. disturbances specific MASLD, occur before symptoms become clinically apparent, therefore be used as diagnosis marker patients.

Language: Английский

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ADAMTS18 deficiency leads to abnormal brain methylation metabolism, dysregulated neuroinflammatory response, and unsound blood-brain barrier structure in mice

Metabolic Brain Disease, Journal Year: 2025, Volume and Issue: 40(4)

Published: April 14, 2025

Language: Английский

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Relationship Between Glucose/Lipid Metabolism and Placental Biomarkers in Gestational Diabetes and Preeclampsia

Diabetes Metabolic Syndrome and Obesity, Journal Year: 2025, Volume and Issue: Volume 18, P. 691 - 702

Published: March 1, 2025

To investigate the significance and relationship of glucose lipid metabolism, placental resistin, human carrier protein (LCN-2) expression in pregnant women with gestational diabetes mellitus (GDM) complicated by severe preeclampsia (SPE). A total 89 patients GDM SPE (G+S group) alone (GDM were included. Blood samples collected to measure metabolism indicators [fasting blood (FBG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), cholesterol (TC), triglycerides (TG), HDL-C, LDL-C], immunohistochemistry was used assess resistin LCN-2 levels. Delivery conditions adverse maternal neonatal outcomes compared. Pearson correlation analysis conducted explore between LCN-2, indicators. FBG, FINS, HbA1c, TC, TG levels higher, HDL-C lower G+S group compared (P<0.05). The positive rates tissue also higher had weeks, birth weight, postpartum hemorrhage than showed (postpartum hemorrhage, intrauterine infection) (preterm birth, fetal distress) that positively correlated TG, negatively Pregnant have risks disorders, expression, patients. Resistin may influence affecting pregnancy outcomes.

Language: Английский

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The Synergistic Roles of Glial Cells and Non-Coding RNAs in the Pathogenesis of Alzheimer’s Disease and Related Dementias (ADRDs)

Neuroglia, Journal Year: 2025, Volume and Issue: 6(2), P. 22 - 22

Published: May 6, 2025

This review synthesizes the emerging understanding of roles glial cells and non-coding RNAs (ncRNAs) in pathogenesis progression Alzheimer’s disease related dementias (ADRDs). ADRDs encompass a spectrum neurodegenerative disorders characterized by cognitive decline, memory impairment, functional deterioration. The interplay between most common types cells—astrocytes, microglia, oligodendrocytes—and ncRNAs is as critical factor development ADRDs. Glial are essential for maintaining homeostasis within central nervous system (CNS); however, their dysregulation can lead to neuroinflammation neuronal dysfunction, exacerbating neurodegeneration. Reactive astrocytes activated microglia create neurotoxic environments that further impair health. Concurrently, ncRNAs, particularly long (lncRNAs) microRNAs (miRNAs), have emerged significant regulators gene expression, influencing inflammatory responses cell function. Understanding complex interactions crucial developing targeted therapeutic strategies. By elucidating mechanisms underlying interactions, this aims highlight importance context diseases, paving way innovative approaches prevent treat Ultimately, enhancing our these processes may novel therapies improved outcomes individuals affected debilitating conditions.

Language: Английский

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Antidepressant Effect of Heracleum moellendorffii Extract on Behavioral Changes in Astrocyte Ablation Mouse Model of Depression by Modulating Neuroinflammation through the Inhibition of Lipocalin-2

Nutrients, Journal Year: 2024, Volume and Issue: 16(13), P. 2049 - 2049

Published: June 27, 2024

Astrocyte dysfunction and inflammation play a pivotal role in depression. In this study, we evaluated the antidepressant properties of Heracleum moellendorffii root extract (HME), which is traditionally used for inflammation-related diseases, mouse model with astrocyte depletion that resembles prefrontal cortex pathology depressive patients. Mice were divided into four groups, 10 mice per group. To induce ablation mice’s (PFC), astrocytic toxin L-alpha-aminoadipic acid (L-AAA) administered HME orally at 200 500 mg/kg 22 days. We utilized tail suspension test (TST) to assess depression-like behaviors open field (OFT) evaluate anxiety-like activities. Additionally, inflammatory markers PFC using immunohistochemistry ELISA. The results showed infusion L-AAA significantly decreased expression glial fibrillary acidic protein (GFAP), was accompanied by increased depression behaviors. However, reversed these effects dose-dependently enhancing GFAP modulating markers, such as TNF-α, IL-6, particularly lipocalin-2, master proinflammatory mediator. These imply contributes alleviation promoting recovery reducing neuroinflammation, especially through lipocalin-2 inhibition.

Language: Английский

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Editorial: An interdisciplinary approach towards a greater understanding of the quality of life in chronic mental illness

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: July 26, 2024

Editorial: An interdisciplinary approach towards a greater understanding of the quality life in chronic mental illness

Language: Английский

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Lipocalin-2 as a therapeutic target for diabetes neurological complications

Expert Opinion on Therapeutic Targets, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 7

Published: Dec. 13, 2024

Diabetes mellitus, a chronic disorder with persistent hyperglycemia, severely affects the quality of life through significant neurological impairments, including neuropathy and cognitive dysfunction. Inflammation oxidative stress are key factors in these complications, Lipocalin-2 (LCN2), which is involved inflammation iron homeostasis, crucial processes.

Language: Английский

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Antidepressant Effects of Ginsenoside Rc on L-Alpha-Aminoadipic Acid-Induced Astrocytic Ablation and Neuroinflammation in Mice

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9673 - 9673

Published: Sept. 6, 2024

Depression is a prevalent and debilitating mental disorder that affects millions worldwide. Current treatments, such as antidepressants targeting the serotonergic system, have limitations, including delayed onset of action high rates treatment resistance, necessitating novel therapeutic strategies. Ginsenoside Rc (G-Rc) has shown potential anti-inflammatory neuroprotective effects, but its antidepressant properties remain unexplored. This study investigated effects G-Rc in an L-alpha-aminoadipic acid (L-AAA)-induced mouse model depression, which mimics astrocytic pathology neuroinflammation observed major depressive disorder. Mice were administered G-Rc, vehicle, or imipramine orally after L-AAA injection into prefrontal cortex. significantly reduced immobility time forced swimming tail suspension tests compared to vehicle treatment, with more pronounced than imipramine. It also attenuated expression pro-inflammatory cytokines (TNF-α, IL-6, TGF-β, lipocalin-2) alleviated degeneration, indicated by increased GFAP decreased IBA-1 levels. Additionally, modulated apoptosis-related proteins, decreasing caspase-3 increasing Bcl-2 levels L-AAA-treated group. These findings suggest exerts regulating neuroinflammation, astrocyte–microglia crosstalk, apoptotic pathways cortex, highlighting agent for depression.

Language: Английский

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