The behavioral, pathological and therapeutic features of the triple transgenic Alzheimer's disease (3 × Tg-AD) mouse model strain

Tian, Sheng; Ye, Tianyuan; Cheng, Xiaorui

doi:10.1016/j.expneurol.2023.114505

Experimental Neurology

2023

DOI: 10.1016/j.expneurol.2023.114505

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The behavioral, pathological and therapeutic features of the triple transgenic Alzheimer's disease (3 × Tg-AD) mouse model strain

Sheng Tian,

Tianyuan Ye,

Xiaorui Cheng

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2024

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Cited by 3 publications

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ACSL3 is a promising therapeutic target for alleviating anxiety and depression in Alzheimer’s disease

Wu,

Zhang,

Howard

et al. 2024

GeroScience

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Alzheimer’s disease (AD), the leading cause of dementia, affects over 55 million people worldwide and is often accompanied by depression and anxiety. Both significantly impact patients’ quality of life and impose substantial societal and economic burdens on healthcare systems. Identifying the complex regulatory mechanisms that contribute to the psychological and emotional deficits in AD will provide promising therapeutic targets. Biosynthesis of omega-3 (ω3) and omega-6 fatty acids (ω6-FA) through long-chain acyl-CoA synthetases (ACSL) is crucial for cell function and survival. This is due to ω3/6-FA’s imperative role in modulating the plasma membrane, energy production, and inflammation. While ACSL dysfunction is known to cause heart, liver, and kidney diseases, the role of ACSL in pathological conditions in the central nervous system (e.g., depression and anxiety) remains largely unexplored. The impact of ACSLs on AD-related depression and anxiety was investigated in a mouse model of Alzheimer’s disease (3xTg-AD). ACSL3 levels were significantly reduced in the hippocampus of aged 3xTg-AD mice (via capillary-based immunoassay). This reduction in ACAL3 was closely associated with increased depression and anxiety-like behavior (via forced swim, tail suspension, elevated plus maze, and sucrose preference test). Upregulation of ACSL3 via adenovirus in aged 3xTg-AD mice led to increased protein levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor C (VEGF-C) (via brain histology, capillary-based immunoassay), resulting in alleviation of depression and anxiety symptoms. The present study highlights a novel neuroprotective role of ACSL3 in the brain. Targeting ACSL3 will offer an innovative approach for treating AD-related depression and anxiety.

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ACSL3 is a promising therapeutic target for alleviating anxiety and depression in Alzheimer’s disease

Wu,

Zhang,

Howard

et al. 2024

GeroScience

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Discovery of a novel Xanthone derivative P24 for anti-AD via targeting sTGFBR3

Zhou,

Qi,

Wang

et al. 2024

European Journal of Medicinal Chemistry

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The Anti-Neuroinflammatory Effect of Extra-Virgin Olive Oil in the Triple Transgenic Mouse Model of Alzheimer’s Disease

Li,

Mutreja,

Servili

et al. 2024

JAD

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Background: Chronic intake of extra virgin olive oil is beneficial for brain health and protects from age-related cognitive decline and dementia, whose most common clinical manifestation is Alzheimer’s disease. Besides the classical pathologic deposits of amyloid beta peptides and phosphorylated tau proteins, another frequent feature of the Alzheimer’s brain is neuroinflammation. Objective: In the current study, we assessed the effect that extra virgin olive oil has on neuroinflammation when administered to a mouse model of the disease. Methods: Triple transgenic mice were randomized to receive a diet enriched with extra virgin olive oil or regular diet for 8 weeks. At the end of this treatment period the expression level of several inflammatory biomarkers was assessed in the central nervous system. Results: Among the 79 biomarkers measured, compared with the control group, mice receiving the extra virgin olive oil had a significant reduction in MIP-2, IL-17E, IL-23, and IL-12p70, but an increase in IL-5. To validate these results, specific ELISA kits were used for each of them. Confirmatory results were obtained for MIP-2, IL-17E, IL-23, and IL-12-p70. No significant differences between the two groups were observed for IL-5. Conclusions: Our results demonstrate that chronic administration of extra virgin olive oil has a potent anti-neuroinflammatory action in a model of Alzheimer’s disease. They provide additional pre-clinical support and novel mechanistic insights for the beneficial effect that this dietary intervention has on brain health and dementia.

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The behavioral, pathological and therapeutic features of the triple transgenic Alzheimer's disease (3 × Tg-AD) mouse model strain

Cited by 3 publications

References 124 publications

ACSL3 is a promising therapeutic target for alleviating anxiety and depression in Alzheimer’s disease

ACSL3 is a promising therapeutic target for alleviating anxiety and depression in Alzheimer’s disease

Discovery of a novel Xanthone derivative P24 for anti-AD via targeting sTGFBR3

The Anti-Neuroinflammatory Effect of Extra-Virgin Olive Oil in the Triple Transgenic Mouse Model of Alzheimer’s Disease

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