Molecular Diversity, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 5, 2024
Language: Английский
Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)
Published: Feb. 21, 2025
Abstract This study investigated the effects of fat mass and obesity-associated (FTO) inhibition on cognitive function metabolic parameters senescence-accelerated mouse prone 8 (SAMP8) mice fed a high-fat diet (HFD). SAMP8 an HFD exhibited increased body weight, impaired glucose tolerance, elevated serum leptin levels. In epididymal white adipose tissue (eWAT), pharmacological treatment with FB23, well-established FTO inhibitor, production modulated genes involved in lipid metabolism (Cpt1a, Atgl , Hsl Fas) oxidative stress (OS) ( Bip Edem ), inflammation (Mcp1, Tnfα) . Expression hepatic related to Mgl, Dgat2, Srebp Plin2) OS (catalase, Edem) were by although steatosis remained unchanged. Remarkably, FB23 m6A RNA methylation brain, accompanied changes N6-methyladenosine (m6A)-regulatory enzymes modulation neuroinflammatory markers (Il6, Mcp1, iNOS) reduced activity matrix metalloproteases (Mmp2, Mmp9) altered IGF1 signaling (Igf1, Pten) Notably, enhanced was observed through expression immediate early (Arc, Fos) transcription factor Stat3 Improved synaptic plasticity evident, as shown levels neurotrophic factors (Bdnf Ngf) restored neurite length spine density. Consistent these findings, behavioral tests demonstrated that effectively rescued impairments mice. The novel object recognition test (NORT) location (OLT) revealed treated short- long-term memory spatial compared control group. Additionally, open field showed reduction anxiety-like behavior after FB23. conclusion, ameliorated HFD-induced disturbances decline These results suggest targeting may be promising therapeutic approach counteract obesity-induced impairment age-related neurodegeneration.
Language: Английский
Citations
3
Toxicology, Journal Year: 2025, Volume and Issue: 515, P. 154164 - 154164
Published: April 24, 2025
Language: Английский
Citations
1
Cellular and Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 44(1)
Published: Oct. 23, 2024
The neurotoxicant trimethyltin (TMT) triggers cognitive impairment and hippocampal neurodegeneration. TMT is a useful research tool for the study of Alzheimer's disease (AD) pathogenesis treatment. Although antidiabetic agent metformin has shown promising neuroprotective effects, however, its precise modes action in neurodegenerative disorders need to be further elucidated. In this study, we investigated whether can mitigate cognition To induce an AD-like phenotype, was injected i.p. (8 mg/kg) administered daily p.o. 3 weeks at 200 mg/kg. Our results showed that administration group mitigated learning memory Barnes maze, novel object recognition (NOR) task, Y attenuated oxidative, inflammatory, cell death/pyroptotic factors, also reversed neurodegeneration-related proteins such as presenilin 1 p-Tau. Hippocampal level AMP-activated protein kinase (AMPK) key regulator energy homeostasis improved following Additionally, reduced acetylcholinesterase (AChE) activity, glial fibrillary acidic (GFAP)-positive reactivity, prevented loss CA1 pyramidal neurons. This TMT-induced neurodegeneration may pave way develop new therapeutics combat against deficits under neurotoxic conditions.
Language: Английский
Citations
4
Gut Microbes, Journal Year: 2025, Volume and Issue: 17(1)
Published: April 10, 2025
The gut-brain axis (GBA) denotes the dynamic and bidirectional communication system that connects gastrointestinal tract central nervous (CNS). This review explored this axis, focusing on role of microbial diversity fitness in maintaining health preventing neurodegeneration, particularly Alzheimer's disease (AD). Gut dysbiosis, characterized by imbalance populations beneficial harmful bacteria, has been associated with increased systemic inflammation, neuroinflammation, progression AD through pathogenic mechanisms involving amyloid deposition, tauopathy, blood-brain barrier (BBB) permeability. Emerging evidence highlighted therapeutic potential probiotics, dietary interventions, intermittent fasting restoring balance, reducing minimizing neurodegenerative risks. Probiotics synbiotics are promising helping improve cognitive function metabolic health, while patterns like Mediterranean diet were linked to decreased neuroinflammation enhanced communication. Despite significant advancement, further research is needed elucidate specific strains, metabolites, influencing brain health. Future studies employing longitudinal designs advanced omics technologies essential developing targeted microbiome-based therapies for managing AD-related disorders.
Language: Английский
Citations
0
Neuropsychiatric Disease and Treatment, Journal Year: 2025, Volume and Issue: Volume 21, P. 927 - 942
Published: April 1, 2025
This study aimed to identify DNA methylation patterns associated with Very Late-Onset Schizophrenia-like Psychosis (VLOSLP) and develop methylation-based biomarkers that differentiate VLOSLP from Schizophrenia (SCZ) Alzheimer's Disease (AD). We analyzed microarray datasets (n = 1218) SCZ AD patients obtained the GEO database. then collected blood samples age-matched healthy controls 80) at Wuxi Mental Health Center for profiling bisulfite sequencing validation. Differential analysis Gene Ontology (GO) enrichment identified candidate loci. prioritized key sites through integrated of quantitative trait loci (meQTL), linkage disequilibrium (LD) patterns, blood-brain correlations. Machine learning algorithms generated diagnostic models, classification performance evaluated using Area Under Curve (AUC) metrics. Analysis revealed distinct signatures in compared controls. The GNB5 gene exhibited shared epigenetic modifications across SCZ, AD, VLOSLP, suggesting a common pathogenic mechanism. model discriminating demonstrated high accuracy, achieving an AUC 1.0 training set 0.958 test (95% CI: 0.875-1.000). versus showed similar robustness, AUCs 0.995 0.955 sets, respectively 0.926-0.983). achieved perfect discrimination (AUC 1.0) both substantial clinical utility. Additional analyses suggested molecular subtypes within VLOSLP. Specific alterations are as potential biomarkers. These findings may contribute development tools, though further validation larger, independent cohorts is warranted.
Language: Английский
Citations
0
Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 19
Published: May 23, 2025
Introduction Learning and memory deficits are clinical characteristics of Alzheimer’s disease (AD), often leading to diminished functionality. The neurotoxicant trimethyltin (TMT) is a valuable research tool for inducing cognitive impairment hippocampal neurodegeneration studying AD pathogenesis treatment. Naringenin flavonoid with potential neuroprotective effects. This study sought investigate the naringenin against induced by TMT neurotoxicity identify some underlying molecular mechanisms. Methods Neurodegeneration was through an 8 mg/kg intraperitoneal injection TMT, followed oral administration (25 100 mg/kg) 21 days. Behavioral assessments, including novel object discrimination (NOD), Y-maze, passive avoidance tests, were carried out evaluate functions. Biochemical assays oxidative/nitrosative stress, mitochondrial membrane (MMP), inflammation, acetylcholinesterase (AChE) enzyme activity, as well pathology-specific markers, conducted. To further validate results, histological assessments CA1 region using Nissl staining immunohistochemical identification 3-nitrotyrosine (3-NT) performed. Results discussion exhibited dose-dependent inhibition neuronal loss reversed TMT-induced deficits. It markedly decreased levels malondialdehyde (MDA), nitrite, tumor necrosis factor-alpha (TNFα), AChE activity while enhancing catalase superoxide dismutase (SOD) activities, immunoreactivity, MMP. Furthermore, findings demonstrated that mitigated elevation in AD-specific proteins, phosphorylated tau (p-tau), amyloid-beta (Aβ), presenilin 1. may be postulated promising therapeutic candidate related neurodegenerative conditions mitigating oxidative nitrosative maintaining integrity, decreasing modulating pathways neurodegeneration.
Language: Английский
Citations
0
Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 102, P. 102556 - 102556
Published: Oct. 30, 2024
Language: Английский
Citations
3
Molecular Diversity, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 5, 2024
Language: Английский
Citations
1