Cognitive Impairment and Synaptic Dysfunction in Cardiovascular Disorders: The New Frontiers of the Heart–Brain Axis

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2387 - 2387

Published: Oct. 18, 2024

Within the central nervous system, synaptic plasticity, fundamental to processes like learning and memory, is largely driven by activity-dependent changes in strength. This plasticity often manifests as long-term potentiation (LTP) depression (LTD), which are bidirectional modulations of efficacy. Strong epidemiological experimental evidence show that heart-brain axis could be severely compromised both neurological cardiovascular disorders. Particularly, disorders, such heart failure, hypertension, obesity, diabetes insulin resistance, arrhythmias, may lead cognitive impairment, a condition known cardiogenic dementia. Herein, we review available knowledge on molecular mechanisms dementia arise describe how LTP and/or LTD induction maintenance CA1 region hippocampus metabolic syndrome, arrhythmias. We also discuss emerging endothelial dysfunction contribute directly altering hippocampal impairing synaptically induced activation nitric oxide synthase. A better understanding CV disorders impact proper function synapses will shed novel light underpinnings dementia, thereby providing new perspective for more specific pharmacological treatments.

Language: Английский

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Obesity-associated memory impairment and neuroinflammation precede widespread peripheral perturbations in aged rats

Immunity & Ageing, Journal Year: 2025, Volume and Issue: 22(1)

Published: Jan. 3, 2025

Obesity and metabolic syndrome are major public health concerns linked to cognitive decline with aging. Prior work from our lab has demonstrated that short-term high fat diet (HFD) rapidly impairs memory function via a neuroinflammatory mechanism. However, the degree which these rapid inflammatory changes unique brain is unknown. Moreover, deviations in gut microbiome composition have been associated obesity impairment, but how aging interact impact microbiome, or occur, less clear. Thus, study investigated of HFD after two distinct consumption durations: 3 months (to model diet-induced obesity) days detect occurring HFD) on function, anxiety-like behavior, central peripheral inflammation, profile young aged rats.

Language: Английский

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Ligature-induced periodontitis in a transgenic mouse model of Alzheimer’s disease dysregulates neuroinflammation, exacerbates cognitive impairment, and accelerates amyloid pathology

Brain Behavior & Immunity - Health, Journal Year: 2025, Volume and Issue: 44, P. 100969 - 100969

Published: Feb. 25, 2025

A growing body of literature has identified periodontal disease among the modifiable risk factors for Alzheimer's (AD), but mechanisms underlying this relationship is unknown. This study investigated using a ligature-induced preclinical periodontitis (Pd) model in non-transgenic (non-Tg) and 3xTg-AD mice. We found that ligature placement caused significant alveolar bone loss, with mice exhibiting exacerbated suggesting AD-related genetic may amplify progression. Pd induced robust local inflammatory gene expression both genotypes, indicated dysregulated immune response. Cognitive deficits were observed only Pd-afflicted mice, specifically hippocampus-mediated spatial memory perirhinal cortex-mediated object recognition memory, while non-Tg remained unaffected. Neuroinflammatory responses varied by brain region, hippocampus prefrontal cortex (PFC) showing most pronounced changes. In these regions, exhibited significantly altered cytokine compared to particularly at later time points. Synaptic markers revealed vulnerabilities including reduced baseline Syp Synpo post-ligature. transiently glutamate receptor persistent changes, potentially linked preserved memory. also accelerated amyloid-β (Aβ) deposition sustained neurodegeneration Overall, shows combining exacerbates inflammation, cognitive impairment, synaptic dysfunction, Aβ pathology, neurodegeneration. Neither insult alone was sufficient produce effects, highlighting synergistic impact. These findings emphasize need explore anti-inflammatory interventions downstream mitigate confluence diseases.

Language: Английский

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Salvianolic acid B (SalB) improves high-fat diet (HFD)-caused cognitive impairment in mice by modulating the Trem2/Dap12 pathway in vivo and in vitro

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 153, P. 114461 - 114461

Published: March 17, 2025

Language: Английский

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A long-term mild high-fat diet facilitates rabbit discrimination learning and alters glycerophospholipid metabolism

Neurobiology of Learning and Memory, Journal Year: 2025, Volume and Issue: unknown, P. 108053 - 108053

Published: April 1, 2025

Language: Английский

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Tetradecyl 2,3-Dihydroxybenzoate Improves Cognitive Function in AD Mice by Modulating Autophagy and Inflammation Through IPA and Hsc70 Targeting

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11719 - 11719

Published: Oct. 31, 2024

Drug development for Alzheimer's disease (AD) treatment is challenging due to its complex pathogenesis. Tetradecyl 2,3-dihydroxybenzoate (ABG-001), a leading compound identified in our prior research, has shown promising NGF-mimicking activity and anti-aging properties. In the present study, both high-fat diet (HFD)-induced AD mice naturally aging were used evaluate anti-AD effects. Meanwhile, RNA-sequences, Western blotting, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), cellular thermal shift (CETSA), drug affinity-responsive target stability (DARTS) assay, construction of expression plasmid protein purification, surface plasmon resonance (SPR) analysis, 16S rRNA sequence analysis identify ABG-001 clarify mechanism action this molecule. effectively mitigates memory dysfunction HFD-induced mice. The therapeutic effect attributed ability promote neurogenesis, activate chaperone-mediated autophagy (CMA), reduce neuronal inflammation. Additionally, positively influenced gut microbiota, enhancing production indole-3-propionic acid (IPA), which capable crossing blood-brain barrier (BBB) contributes regeneration. Furthermore, research revealed that IPA, linked properties ABG-001, targets heat shock cognate 70 kDa (Hsc70) regulates Hsc70/PKM2/HK2/LC3 FOXO3a/SIRT1 signaling pathways. improves by modulating inflammation through IPA Hsc70 targeting. These findings offer novel approach treating neurodegenerative diseases, focusing on modification microbiota metabolites coupled with strategies.

Language: Английский

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