Understanding Epigenetics in the Neurodegeneration of Alzheimer’s Disease: SAMP8 Mouse Model

Griñán-Ferré, Christian; Corpas, Rubén; Palomera-Ávalos, Verónica; Sanfeliu, Coral; Pallàs, Mercè

doi:10.3233/jad-170664

Cited by 66 publications

(63 citation statements)

References 249 publications

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“…As an important in vivo model in senescence-accelerated proneness, SAMP8 mice present age-related cognitive deterioration (Griñan-Ferré et al, 2016;Akiguchi et al, 2017) and show pathological features similar to the mechanisms responsible for AD pathophysiology, such as oxidative stress, APP overexpression, Aβ deposition and tau phosphorylation (Li et al, 2013;Bayod et al, 2014;Cheng et al, 2014). SAMP8 is a good animal model to investigate the fundamental mechanisms of age-related learning and memory deficits and is widely used for studying early neurodegenerative changes, associated with AD (Butterfield and Poon, 2005;Manich et al, 2011;Griñán-Ferré et al, 2018). This study assessed changes in SAMP8 mice hippocampal neurovascular pathway and compared them to the normal aging process in the control senescence-accelerated resistant 1 (SAMR1) mice (Takeda, 2009).…”

Section: Introductionmentioning

confidence: 99%

Benign Regulation of the Astrocytic Phospholipase A2-Arachidonic Acid Pathway: The Underlying Mechanism of the Beneficial Effects of Manual Acupuncture on CBF

et al. 2020

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Background: The astrocytic phospholipase A 2 (PLA 2 )-arachidonic acid (AA) pathway is crucial in understanding the reduction of cerebral blood flow (CBF) prior to cognitive deterioration. In complementary and alternative medicine, manual acupuncture (MA) is used as one of the most important therapies for Alzheimer's disease (AD). The beneficial effects of MA on CBF were reported in our previous study. However, the underlying molecular mechanism remains largely elusive.Objective: To investigate the effect of MA on the astrocytic PLA 2 -AA pathway in SAMP8 mice hippocampi.Methods: SAMP8 mice were divided into the SAMP8 control (Pc) group, the SAMP8 MA (Pm) group and the SAMP8 donepezil (Pd) group. SAMR1 mice were used as the SAMRl control (Rc) group. Mice in the Pd group were treated with donepezil hydrochloride at 0.65 µg/g. In the Pm group, MA was applied at Baihui (GV20) and Yintang (GV29) for 20 min. The above treatments were administered once a day for 26 consecutive days. The Morris water maze was applied to assess spatial learning and memory. Immunofluorescence staining, western blot and liquid chromatographytandem mass spectrometry were used to investigate the expression of related proteins and measure the contents of the metabolic intermediates of the PLA 2 -AA pathway.Results: Compared with that in the Rc group, the escape latency in the Pc group significantly increased (p < 0.01); whereas, the platform crossover number and percentage of time and swimming distance in the platform quadrant decreased (p < 0.01). The hippocampal expression of PLA 2 , cyclooxygenase-1, cytochrome P450 proteins 2C23 and the levels of AA, prostaglandin E 2 and epoxyeicosatrienoic acids of the Pc group was drastically higher than that in the Rc group (p < 0.01). These changes were reversed by MA and donepezil (p < 0.01 or p < 0.05). Frontiers in Neuroscience | www.frontiersin.org February 2020 | Volume 13 | Article 1354 Ding et al. Acupuncture Regulates PLA 2 -AA PathwayConclusion: MA can effectively improve the learning and memory abilities of SAMP8 mice and has a negative regulatory effect on the PLA 2 -AA pathway. We propose that the increase of the arterial tone, which is induced by the inhibition of vasodilatory pathway, may be a reason for the beneficial effect of MA on CBF.Keywords: manual acupuncture, Alzheimer's disease, astrocyte, hippocampus, phospholipase A 2 , arachidonic acid, cerebral blood flow absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Section: Introductionmentioning

confidence: 99%

Benign Regulation of the Astrocytic Phospholipase A2-Arachidonic Acid Pathway: The Underlying Mechanism of the Beneficial Effects of Manual Acupuncture on CBF

et al. 2020

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“…In particular, chronic stress is associated with increased Aβ deposits and hyperphosphorylated Tau [13].Oxidative stress (OS) and inflammation are deeply involved in age-related deleterious disorders. Along with the aging process, several factors, such as a naturally decreased capacity of the antioxidant enzymes system, create an imbalance between antioxidant mechanisms and reactive oxygen system (ROS)-production equilibrium, accumulating ROS beyond the detoxifying capacity of the antioxidant system resulting in OS, eventually causing cellular damage that can no longer be repaired by internal mechanisms, and finally causing dysfunction of the system [14]. In addition, one of the major changes during aging is the dysregulation of the immune response, leading to chronic systemic inflammatory state [15].…”

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confidence: 99%

“…In addition, one of the major changes during aging is the dysregulation of the immune response, leading to chronic systemic inflammatory state [15]. Overall, OS imbalance, mitochondrial dysfunction and the inflammatory response have been linked to accelerated aging and faster progression of neurodegenerative diseases [14,16]. Moreover, the accumulation of dysfunctional and damaged cellular proteins and organelles occurs during aging, resulting in a disruption of cellular homeostasis and progressive degeneration and increases the risk of cell death [17].…”

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confidence: 99%

Chronic Mild Stress Modified Epigenetic Mechanisms Leading to Accelerated Senescence and Impaired Cognitive Performance in Mice

Puigoriol-Illamola

Martínez-Damas

Pallàs

2020

IJMS

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Cognitive and behavioural disturbances are a growing public healthcare issue for the modern society, as stressful lifestyle is becoming more and more common. Besides, several pieces of evidence state that environment is crucial in the development of several diseases as well as compromising healthy aging. Therefore, it is important to study the effects of stress on cognition and its relationship with aging. To address these queries, Chronic Mild Stress (CMS) paradigm was used in the senescence-accelerated mouse prone 8 (SAMP8) and resistant 1 (SAMR1). On one hand, we determined the changes produced in the three main epigenetic marks after 4 weeks of CMS treatment, such as a reduction in histone posttranslational modifications and DNA methylation, and up-regulation or down-regulation of several miRNA involved in different cellular processes in mice. In addition, CMS treatment induced reactive oxygen species (ROS) damage accumulation and loss of antioxidant defence mechanisms, as well as inflammatory signalling activation through NF-κB pathway and astrogliosis markers, like Gfap. Remarkably, CMS altered mTORC1 signalling in both strains, decreasing autophagy only in SAMR1 mice. We found a decrease in glycogen synthase kinase 3 β (GSK-3β) inactivation, hyperphosphorylation of Tau and an increase in sAPPβ protein levels in mice under CMS. Moreover, reduction in the non-amyloidogenic secretase ADAM10 protein levels was found in SAMR1 CMS group. Consequently, detrimental effects on behaviour and cognitive performance were detected in CMS treated mice, affecting mainly SAMR1 mice, promoting a turning to SAMP8 phenotype. In conclusion, CMS is a feasible intervention to understand the influence of stress on epigenetic mechanisms underlying cognition and accelerating senescence.responses to different stimulus [1]. Indeed, normal aging differs from pathological aging and this might be explained by the lifestyle. Environmental factors drive epigenetic modifications, resulting in phenotypic differences, which alter almost all tissues and organs. Although the brain is one of the most affected structures, such modifications lead to a progressive decline in the cognitive function and create a favourable context for the development of neurodegenerative diseases [2]. Aging is the most significant risk factor for most chronic diseases, such as age-related cognitive decline and Alzheimer's disease (AD) [3]. In fact, AD is the most prevalent dementia and its progression is influenced by both genetic and environmental factors [4].Several studies define that a good environment is essential to enhance learning and cognitive abilities, besides the continued presence of stressors being associated with the opposite effects. Epigenetics refers to potentially heritable and environmentally modifiable changes in gene expression mediated via non-DNA encoded mechanisms [5]. Recent evidence has demonstrated significant associations between epigenetic alterations and stress [2,6]. Potential threats cause a course of action releasing numerous transm...

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“…These SAMP8 mice are also used to study brain aging and neurodegeneration (8). While these mice are an accepted model to investigate the aging process, most phenotypes in the SAMP8 mice are not fully explained by genetic factors (9). In contrast, the Senescent-Accelerated Mouse-Resistant 1 (SAMR1) model, with a similar genetic background to SAMP8 mice, has been used as an appropriate control model displaying normal aging characteristics.…”

Section: Introductionmentioning

confidence: 99%

Effect of olive oil consumption on aging in a senescence-accelerated mice-prone 8 (SAMP8) model

et al. 2019

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Background : Mediterranean diets have been linked to a reduced risk of cancer, vascular illnesses, Parkinson's and Alzheimer's disease. Olive oil is the primary fat source in the Mediterranean diet ; however, only a few studies have investigated the effect of olive oil on aging. In the present study, we aimed to determine whether consumption of olive oil significantly influences aging and memory in senescence-accelerated mouse-prone 8 (SAMP8). Methods : SAMP8 and senescence-accelerated mouse resistant 1 (SAMR1) mice were fed either 7% soy oil or 1% olive oil and 6% soy oil during a six-month study period. Reduction in memory in passive avoidance learning was examined after two months from the initiation of the experiment. Results : The weight of organs including the liver, kidney, spleen, and fat tissue changed significantly and memory performance was reduced in SAMP8 than in SAMR1 mice. There were no significant differences in SAMP8 and SAMR1 mice; however, blood triglyceride level decreased significantly in SAMP8 mice fed on olive oil. Conclusions : These results suggest that consuming olive oil may not have a protective role in aging and memory recall, but beneficial effects may be related to improvement in lipid metabolism. J. Med. Invest. 66 : 241-247, August, 2019

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Understanding Epigenetics in the Neurodegeneration of Alzheimer’s Disease: SAMP8 Mouse Model

Cited by 66 publications

References 249 publications

Benign Regulation of the Astrocytic Phospholipase A2-Arachidonic Acid Pathway: The Underlying Mechanism of the Beneficial Effects of Manual Acupuncture on CBF

Benign Regulation of the Astrocytic Phospholipase A2-Arachidonic Acid Pathway: The Underlying Mechanism of the Beneficial Effects of Manual Acupuncture on CBF

Chronic Mild Stress Modified Epigenetic Mechanisms Leading to Accelerated Senescence and Impaired Cognitive Performance in Mice

Effect of olive oil consumption on aging in a senescence-accelerated mice-prone 8 (SAMP8) model

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