DNA methylation is necessary for erythropoietin to improve spatial learning and memory in SAMP8 mice

Yu, Nengwei; Liu, Jie; Ye, Gang; Ye, Fang; Xiao, Jun; Guo, Fei

doi:10.1016/j.exger.2015.06.009

Cited by 4 publications

(4 citation statements)

References 36 publications

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“…It has been published that expression of Dnmt3b was increased in SAMP8 after injection of erythropoietin improving spatial learning and memory, indicating that the methylation state of DNA is necessary for learning and memory, including the memory formation [ 243 ]. Epigenetic mechanisms underlying cognitive impairment by accelerated aging in SAMP8 were also found in an AD mice model, as 5xFAD, where Aβ is a key factor in cognitive impairment and neurodegeneration [ 233, 244 ].…”

Section: Samp8 Mouse Modelmentioning

confidence: 99%

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

Griñán-Ferré

Corpas

Palomera-Ávalos

et al. 2018

JAD

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Epigenetics is emerging as the missing link among genetic inheritance, environmental influences, and body and brain health status. In the brain, specific changes in nucleic acids or their associated proteins in neurons and glial cells might imprint differential patterns of gene activation that will favor either cognitive enhancement or cognitive loss for more than one generation. Furthermore, derangement of age-related epigenetic signaling is appearing as a significant risk factor for illnesses of aging, including neurodegeneration and Alzheimer’s disease (AD). In addition, better knowledge of epigenetic mechanisms might provide hints and clues in the triggering and progression of AD. Intense research in experimental models suggests that molecular interventions for modulating epigenetic mechanisms might have therapeutic applications to promote cognitive maintenance through an advanced age. The SAMP8 mouse is a senescence model with AD traits in which the study of epigenetic alterations may unveil epigenetic therapies against the AD.

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Section: Samp8 Mouse Modelmentioning

confidence: 99%

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

Griñán-Ferré

Corpas

Palomera-Ávalos

et al. 2018

JAD

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“…Proper function of the brain is multifactorial and among those parameters critical to cognition are epigenetic mechanisms, particularly DNA methylation and histone modifications. In recent years, the field of neuroepigenetics has seen significant advancements 6 7 and compelling evidence suggests that persistent changes in DNA methylation may significantly impact learning and memory 8 9 10 11 12 13 . Specifically, rats treated with 5-azadeoxycytidine (5-aza) or zebularine (zeb) to inhibit DNA methyltransferase (DNMT) enzyme activity, or with the direct DNMT inhibitor RG108, failed to display normal memory stability 8 , reward learning 9 , or spatial learning and memory 10 11 .…”

mentioning

confidence: 99%

“…In recent years, the field of neuroepigenetics has seen significant advancements 6 7 and compelling evidence suggests that persistent changes in DNA methylation may significantly impact learning and memory 8 9 10 11 12 13 . Specifically, rats treated with 5-azadeoxycytidine (5-aza) or zebularine (zeb) to inhibit DNA methyltransferase (DNMT) enzyme activity, or with the direct DNMT inhibitor RG108, failed to display normal memory stability 8 , reward learning 9 , or spatial learning and memory 10 11 . Using a different approach to manipulate DNA methylation, another study provided evidence that animals maintained on a methyl donor deficient diet exhibited altered expression of glutamate receptor related genes, as well as impaired novel object recognition and fear extinction 13 .…”

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confidence: 99%

Epigenetic determinants of space radiation-induced cognitive dysfunction

Acharya

Baddour

Kawashita

et al. 2017

Sci Rep

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Among the dangers to astronauts engaging in deep space missions such as a Mars expedition is exposure to radiations that put them at risk for severe cognitive dysfunction. These radiation-induced cognitive impairments are accompanied by functional and structural changes including oxidative stress, neuroinflammation, and degradation of neuronal architecture. The molecular mechanisms that dictate CNS function are multifaceted and it is unclear how irradiation induces persistent alterations in the brain. Among those determinants of cognitive function are neuroepigenetic mechanisms that translate radiation responses into altered gene expression and cellular phenotype. In this study, we have demonstrated a correlation between epigenetic aberrations and adverse effects of space relevant irradiation on cognition. In cognitively impaired irradiated mice we observed increased 5-methylcytosine and 5-hydroxymethylcytosine levels in the hippocampus that coincided with increased levels of the DNA methylating enzymes DNMT3a, TET1 and TET3. By inhibiting methylation using 5-iodotubercidin, we demonstrated amelioration of the epigenetic effects of irradiation. In addition to protecting against those molecular effects of irradiation, 5-iodotubercidin restored behavioral performance to that of unirradiated animals. The findings of this study establish the possibility that neuroepigenetic mechanisms significantly contribute to the functional and structural changes that affect the irradiated brain and cognition.

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“…Suicide attempters were linked to Dnmt3b SNP polymorphisms [9]. EPO micro-injected into the hippocampus upregulated Dnmt3b expression and improved spatial learning & memory in SAMP8 mice [10]. However, its molecular and cellular mechanisms remain unclear.…”

mentioning

confidence: 99%

Conditional Dnmt3b deletion in hippocampal dCA1 impairs recognition memory

Kong

Zhang

et al. 2020

Mol Brain

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Aim: Active changes in neuronal DNA methylation and demethylation appear to act as controllers of synaptic scaling and glutamate receptor trafficking in learning and memory formation. DNA methyltransferases (DNMTs), including proteins encoded by Dnmt1, Dnmt3a and Dnmt3b, are dominant enzymes carrying out DNA methylation. Our previous study demonstrated the important roles that DNMT1 and DNMT3a play in synaptic function and memory. In this study, we aim to explore the role of DNMT3b and its-mediated DNA methylation in memory processes. Methods: Dnmt3b was knocked down specifically in dorsal CA1 neurons of adult mice hippocampus by AAV-syn-Cre-GFP virus injection. Behavioral tests were used to evaluate memory performance. Gene expression microarray analysis followed by quantitative RT-PCR were performed to find differential expression genes. Results: Dnmt3b flox/flox mice receiving Cre-virus infection showed impaired novel object-place recognition (NPR) and normal novel object recognition (NOR), in comparison to mice receiving control GFP-virus infection. Microarray analysis revealed differential expression of K + channel subunits in the hippocampus of Dnmt3b flox/flox mice receiving Cre-virus injection. Increased Kcne2 expression was confirmed by following qRT-PCR analysis. We also found that NPR training and testing induced up-regulation of hippocampal Dnmt1 and Dnmt3a mRNA expression in control mice, but not in Cre-virus injected mice. Our findings thus demonstrate that conditional Dnmt3b deletion in a subregion of the hippocampus impairs a specific form of recognition memory that is hippocampus-dependent.

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DNA methylation is necessary for erythropoietin to improve spatial learning and memory in SAMP8 mice

Cited by 4 publications

References 36 publications

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

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

Epigenetic determinants of space radiation-induced cognitive dysfunction

Conditional Dnmt3b deletion in hippocampal dCA1 impairs recognition memory

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