Alzheimer-like brain metabolic and structural features in cholesterol-fed rabbit detected by magnetic resonance imaging

Jin, Ping; Pan, Yongming; Pan, Zhi-Yong; Xu, Jianqin; Lin, Min; Sun, Zhichao; Chen, Minli; Xu, Maosheng

doi:10.1186/s12944-018-0705-9

Cited by 16 publications

(15 citation statements)

References 44 publications

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“…Afflictions to the brain are linked with metabolic alterations generated by obesity. These afflictions could prompt neuronal death, either by apoptosis or cell necrosis, in addition to changes in the neuron’s synaptic plasticity [ 4 , 5 ]. Obesity now is ranked as the fifth leading cause of death worldwide, and its global spread is alarming [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Inflated levels of pro-inflammatory cytokines elevate inflammation that consecutively induces cognitive deficiency [ 10 , 11 ]. The abundant increase of visceral adipose tissue is affiliated with obesity, specifically in adipocyte size, and this elevation extremely impacts the adipose tissue performance [ 5 , 12 ]. White adipose tissue excretes an assortment of pro-inflammatory and anti-inflammatory factors [ 12 ], among them are the adipokines (adiponectin and leptin) and cytokines [ 5 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Thymoquinone Protects Neurons in the Cerebellum of Rats through Mitigating Oxidative Stress and Inflammation Following High-Fat Diet Supplementation

Alrafiah

2021

Biomolecules

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High-fat diet (HFD) is a major problem causing neuronal damage. Thymoquinone (TQ) could regulate oxidative stress and the inflammatory process. Hence, the present study elucidated the significant role of TQ on oxidative stress, inflammation, as well as morphological changes in the cerebellum of rats with HFD. Rats were divided into three groups as (1) control, (2) saturated HFD for eight weeks and (3) HFD supplementation (four weeks) followed by TQ 300 mg/kg/day treated (four weeks). After treatment, blood samples were collected to measure oxidative stress markers glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and inflammatory cytokines. Furthermore, neuronal morphological changes were also observed in the cerebellum of the rats. HFD rats show higher body weight (286.5 ± 7.4 g) as compared with the control group (224.67 ± 1.78 g). TQ treatment significantly (p < 0.05) lowered the body weight (225.83 ± 13.15 g). TQ produced a significant (p < 0.05) reduction in cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). The antioxidative enzymes significantly reduced in HFD rats (GSH, 1.46 ± 0.36 mol/L and SOD, 99.13 ± 5.41 µmol/mL) as compared with the control group (GSH, 6.25 ± 0.36 mol/L and SOD, 159.67 ± 10.67 µmol/mL). MDA was increased significantly in HFD rats (2.05 ± 0.25 nmol/L) compared to the control group (0.695 ± 0.11 nmol/L). Surprisingly, treatment with TQ could improve the level of GSH, MDA, and SOD. TQ treatment significantly (p < 0.05) reduced the inflammatory markers as compared with HFD alone. TQ treatment minimizes neuronal damage as well as reduces inflammation and improves antioxidant enzymes. TQ can be considered as a promising agent in preventing the neuronal morphological changes in the cerebellum of obese populations.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thymoquinone Protects Neurons in the Cerebellum of Rats through Mitigating Oxidative Stress and Inflammation Following High-Fat Diet Supplementation

Alrafiah

2021

Biomolecules

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“…Studies in mice show that accumulation of neuronal cholesterol caused a respective 3.4 ± 0.7-fold and a 1.6 ± 0.14-fold increase in Aβ-C terminal fragment and Aβ42 in the hippocampus (Djelti et al, 2015). Similarly, rabbits fed a 2% cholesterol diet displayed a significant increase Aβ42 levels in both cortex and hippocampus (P. Jin et al, 2018). However, epidemiological studies and human data from serum/plasma or brain indicating an association between high cholesterol and AD have been highly inconsistent (Wood, Li, Muller, & Eckert, 2014).…”

Section: Cardiovascular Risk Factorsmentioning

confidence: 93%

Gene-environment interactions in Alzheimer's disease: A potential path to precision medicine

Eid

Mhatre

Richardson

2019

Pharmacology & Therapeutics

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Alzheimer's disease (AD) is the leading cause of dementia in the United States and afflicts greater than 5.7 million Americans in 2018. Therapeutic options remain extremely limited to those that are symptom targeting, while no drugs have been approved for the modification or reversal of the disease itself. Risk factors for AD including aging, the female sex, as well as carrying an APOE4 genotype. These risk factors have been extensively examined in the literature, while less attention has been paid to modifiable risk factors, including lifestyle, and environmental risk factors such as exposures to air pollution and pesticides. This review highlights the most recent data on risk factors in AD and identifies gene by environment interactions that have been investigated. It also provides a suggested framework for a personalized therapeutic approach to AD, by combining genetic, environmental and lifestyle risk factors. Understanding modifiable risk factors and their interaction with non-modifiable factors (age, susceptibility alleles, and sex) is paramount for designing personalized therapeutic interventions.

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“…Certainly, some studies indicate that brain cholesterol levels may be raised in AD, compared to non-demented, brains (Kivipelto et al, 2001;Xiong et al, 2008;Jin et al, 2018;Wingo et al, 2019), although not all studies concur (Ledesma & Dotti, 2005). That cholesterol may be directly associated with amyloid plaque formation is supported by brain imaging studies, which show Aβ collocated with cholesterol within amyloid deposits in brain samples from AD-affected humans and other species (Mori et al, 2001;Burns et al, 2003;Xiong et al, 2008).…”

Section: The Role Of Excess Cholesterol In Amyloidogenesismentioning

confidence: 99%

A lipid-leakage model for Alzheimer’s Disease

Rudge

2019

Preprint

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This paper describes a potential new explanation for Alzheimer’s disease (AD), referred to here as the lipid-leakage model. It proposes that AD is caused by the influx of lipids following the breakdown of the blood brain barrier (BBB). The model argues that a principle role of the BBB is to protect the brain from external lipid access. When the BBB is damaged, it allows a mass influx of (mainly albumin-bound) free fatty acids (FFAs) and lipid-rich lipoproteins to the brain, which in turn causes neurodegeneration, amyloidosis, tau tangles and other AD characteristics. The model also argues that, whilst β-amyloid causes neurodegeneration, as is widely argued, its principal role in the disease lies in damaging the BBB. It is the external lipids, entering as a consequence, that are the primary drivers of neurodegeneration in AD., especially FFAs, which induce oxidative stress, stimulate microglia-driven neuroinflammation, and inhibit neurogenesis. Simultaneously, the larger, more lipid-laden lipoproteins, characteristic of the external plasma but not the CNS, cause endosomal-lysosomal abnormalities, amyloidosis and the formation of tau tangles, all characteristic of AD. In most cases (certainly in late-onset, noninherited forms of the disease) amyloidosis and tau tangle formation are consequences of this external lipid invasion, and in many ways more symptomatic of the disease than causative. In support of this, it is argued that the pattern of damage caused by the influx of FFAs into the brain is likely to resemble the neurodegeneration seen in alcohol-related brain damage (ARBD), a disease that shows many similarities to AD, including the areas of the brain it affects. The fact that neurodegeneration is far more pronounced in AD than in ARBD most likely results from the greater heterogeneity of the lipid assault in AD compared with ethanol alone. The lipid-leakage model, described here, arguably provides the first cohesive, multi-factorial explanation of AD that best accounts for all currently known major risk factors, and credibly explains all AD-associated pathologies, including those, such as endosomal-lysosomal dysfunction and excessive lipid droplet formation, that have been too readily overlooked by other accounts of this disease.

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Alzheimer-like brain metabolic and structural features in cholesterol-fed rabbit detected by magnetic resonance imaging

Cited by 16 publications

References 44 publications

Thymoquinone Protects Neurons in the Cerebellum of Rats through Mitigating Oxidative Stress and Inflammation Following High-Fat Diet Supplementation

Thymoquinone Protects Neurons in the Cerebellum of Rats through Mitigating Oxidative Stress and Inflammation Following High-Fat Diet Supplementation

Gene-environment interactions in Alzheimer's disease: A potential path to precision medicine

A lipid-leakage model for Alzheimer’s Disease

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