The behavioral, pathological and therapeutic features of the senescence-accelerated mouse prone 8 strain as an Alzheimer's disease animal model

Cheng, Xiaorui; Zhou, Wen; Zhang, Yongxiang

doi:10.1016/j.arr.2013.10.002

Cited by 114 publications

(79 citation statements)

References 216 publications

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“…SAMP8 mice exhibit accelerated senescence and have been proposed to be a model of AD [15]. This strain has early onset age-associated impairments of spatial learning and memory in hippocampus-dependent tests (such as the Morris water maze test) [15] and experienced numerous AD-like pathological symptoms, such as increased Aβ production, hyperphosphorylation of tau protein and AChE activity as well as a decline in hippocampal synaptic transmission and long-term potentiation [16][17][18][19]. Our data were partially consistent with the studies by Cheng S [20], Dobarro M [21], and XiYang YB [22], which demonstrated that SAMP8 mice showed visual recognition impairment in the novel object recognition test, impairment of spontaneous alternation behavior in the Y-maze test, and spatial memory impairment in the Morris water maze test from the training session to the probe test.…”

Section: Discussionmentioning

confidence: 99%

Silibinin rescues learning and memory deficits by attenuating microglia activation and preventing neuroinflammatory reactions in SAMP8 mice

Jin

Bai

Yin

et al. 2016

Neuroscience Letters

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Section: Discussionmentioning

confidence: 99%

Silibinin rescues learning and memory deficits by attenuating microglia activation and preventing neuroinflammatory reactions in SAMP8 mice

Jin

Bai

Yin

et al. 2016

Neuroscience Letters

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“…EE also increases behavioral performance when memory is evaluated by NORT [35,36]. SAMP8 has been studied as a nontransgenic murine model for accelerated senescence and late-onset AD [20][21][22][23]37]. These mice exhibited cognitive and emotional disturbances from young ages, probably due to brain pathological hallmarks such as OS, inflammation, and activated neuronal death pathways, mainly affecting cortex and hippocampus.…”

Section: Samp8mentioning

confidence: 98%

Environmental Enrichment Improves Behavior, Cognition, and Brain Functional Markers in Young Senescence-Accelerated Prone Mice (SAMP8)

et al. 2015

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The environment in which organisms live can greatly influence their development. Consequently, environmental enrichment (EE) is progressively recognized as an important component in the improvement of brain function and development. It has been demonstrated that rodents raised under EE conditions exhibit favorable neuroanatomical effects that improve their learning, spatial memory, and behavioral performance. Here, by using senescence-accelerated prone mice (SAMP8) and these as a model of adverse genetic conditions for brain development, we determined the effect of EE by raising these mice during early life under favorable conditions. We found a better generalized performance of SAMP8 under EE in the results of four behavioral and learning tests. In addition, we demonstrated broad molecular correlation in the hippocampus by an increase in NeuN and Ki67 expression, as well as an increase in the expression of neurotrophic factors, such as pleiotrophin (PTN) and brain-derived neurotrophic factor (BDNF), with a parallel decrease in neurodegenerative markers such as GSK3, amyloid-beta precursor protein, and phosphorylated beta-catenin, and a reduction of SBDP120, Bax, GFAP, and interleukin-6 (IL-6), resulting in a neuroprotective panorama. Globally, it can be concluded that EE applied to SAMP8 at young ages resulted in epigenetic regulatory mechanisms that give rise to significant beneficial effects at the molecular, cellular, and behavioral levels during brain development, particularly in the hippocampus.

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“…The SAMP8 strain (P8) was selected from AKR/J mice and is a well-characterized model for studying pathological brain aging [18-21]. The SAMR1 mice (R1), with a similar genetic background and normal aging characteristics, represent a suitable and widely used control model [22].…”

Section: Introductionmentioning

confidence: 99%

“…P8 mice presented signs of accelerated aging such as loss of activity, skin coarseness, alopecia, lack of hair glossiness, increased lordokyphosis, periophthalmic lesions, and systemic senile amyloidosis [23]. These mice also displayed cognitive and behavioral alterations that were accompanied by molecular features typical of Alzheimer’s disease (AD), such as overproduction of amyloid-beta protein, increased tau phosphorylation, cholinergic deficits in the forebrain and increased oxidative stress [18,19,24-28]. Biomarkers of inflammation such as C-reactive protein and serum amyloid P are elevated in P8 mice [29].…”

Section: Introductionmentioning

confidence: 99%

Rcor2 underexpression in senescent mice: a target for inflammaging?

Álvarez-López

Molina-Martínez

Castro

et al. 2014

J Neuroinflammation

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BackgroundAging is characterized by a low-grade systemic inflammation that contributes to the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease (AD). However, little knowledge is currently available on the molecular processes leading to chronic neuroinflammation. In this context, recent studies have described the role of chromatin regulators in inflammation and longevity including the REST corepressor (Rcor)-2 factor, which seems to be involved in an inflammatory suppressive program.MethodsTo assess the impact of Rcor2 in age-related inflammation, gene expression levels were quantified in different tissues and ages of the spontaneous senescence-accelerated P8 mouse (P8) using the SAMR1 mouse (R1) as a control. Specific siRNA transfection in P8 and R1 astrocyte cultures was used to determine Rcor2 involvement in the modulation of neuroinflammation. The effect of lipopolysaccharide (LPS) treatment on Rcor2 levels and neuroinflammation was analyzed both in vivo and in vitro.ResultsP8 mice presented a dramatic decrease in Rcor2 gene expression compared with R1 controls in splenocytes, an alteration also observed in the brain cortex, hippocampus and primary astrocytes of these mice. Rcor2 reduction in astrocytes was accompanied by an increased basal expression of the interleukin (Il)-6 gene. Strikingly, intraperitoneal LPS injection in R1 mice downregulated Rcor2 in the hippocampus, with a concomitant upregulation of tumor necrosis factor (Tnf-α), Il1-β and Il6 genes. A negative correlation between Rcor2 and Il6 gene expression was also verified in LPS-treated C6 glioma cells. Knock down of Rcor2 by siRNA transfection (siRcor2) in R1 astrocytes upregulated Il6 gene expression while siRcor2 further increased Il6 expression in P8 astrocytes. Moreover, LPS activation provoked a further downregulation of Rcor2 and an amplified induction of Il6 in siRcor2-tranfected astrocytes.ConclusionsData presented here show interplay between Rcor2 downregulation and increased inflammation and suggest that Rcor2 may be a key regulator of inflammaging.

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The behavioral, pathological and therapeutic features of the senescence-accelerated mouse prone 8 strain as an Alzheimer's disease animal model

Cited by 114 publications

References 216 publications

Silibinin rescues learning and memory deficits by attenuating microglia activation and preventing neuroinflammatory reactions in SAMP8 mice

Silibinin rescues learning and memory deficits by attenuating microglia activation and preventing neuroinflammatory reactions in SAMP8 mice

Environmental Enrichment Improves Behavior, Cognition, and Brain Functional Markers in Young Senescence-Accelerated Prone Mice (SAMP8)

Rcor2 underexpression in senescent mice: a target for inflammaging?

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