<i>MEF2C</i> mRNA expression and cognitive function in Japanese patients with Alzheimer's disease

Sao, Tomoko; Yoshino, Yuta; Yamazaki, Kiyohiro; Ozaki, Yuki; Mori, Yoko; Ochi, Shinichiro; Yoshida, Taku; Mori, Takaaki; Iga, Jun‐ichi; Ueno, Shu‐ichi

doi:10.1111/pcn.12618

Cited by 39 publications

(28 citation statements)

References 53 publications

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“…While some studies showed the opposite results. The mRNA expression of MEF2C was low in Alzheimer's Diseases patients, but Sao et al found no correlation between the methylation level of promoter and mRNA expression of MEF2C. Tsumagari et al found that the hypermethylation of the promoter region was correlated with the higher expression of TBX1 in mononuclear myoblasts and multinuclear myotubes.…”

Section: Discussionmentioning

confidence: 99%

Impact of DNA methyltransferase inhibitor 5‐azacytidine on cardiac development of zebrafish in vivo and cardiomyocyte proliferation, apoptosis, and the homeostasis of gene expression in vitro

Yang

Wang

et al. 2019

J of Cellular Biochemistry

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Cardiac development is a peculiar process involving coordinated cellular differentiation, migration, proliferation, and apoptosis. DNA methylation plays a key role in genomic stability, tissue‐specific gene expression, cell proliferation, and apoptosis. Hypomethylation in the global genome has been reported in cardiovascular diseases. However, little is known about the impact and specific mechanism of global hypomethylation on cardiomyocytes. In the present study, we explored the impact of DNA methyltransferase inhibitors 5‐azacytidine on cardiac development. In vivo experiment showed that hypomethylation of zebrafish embryos with 5‐azacytidine exposure significantly reduced survival, induced malformations, and delayed general development process. Furthermore, zebrafish embryos injected with 5‐azacytidine developed pericardial edema, ventricular volume reduction, looping deformity, and reduction in heart rate and ventricular shortening fraction. Cardiomyocytes treated with 5‐azacytidine in vitro decreased proliferation and induced apoptosis in a concentration‐dependent manner. Furthermore, 5‐azacytidine treatment in cardiomyocytes resulted in 20 downregulated genes expression and two upregulated genes expression in 45 candidate genes, which indicated that DNA methylation functions as a bidirectional modulator in regulating gene expression. In conclusion, these results show the regulative effects of the epigenetic modifier 5‐azacytidine in cardiac development of zebrafish embryos in vivo and cardiomyocyte proliferation and apoptosis and the homeostasis of gene expression in vitro, which offer a novel understanding of aberrant DNA methylation in the etiology of cardiovascular disease.

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Section: Discussionmentioning

confidence: 99%

Impact of DNA methyltransferase inhibitor 5‐azacytidine on cardiac development of zebrafish in vivo and cardiomyocyte proliferation, apoptosis, and the homeostasis of gene expression in vitro

Yang

Wang

et al. 2019

J of Cellular Biochemistry

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“…Our list of previously published blood transcriptome biomarkers of AD is shown in Table 4 [7][8][9][10][11][12][13][14][15]. The Trem1 mRNA levels tended to increase with age only in the control mouse blood.…”

Section: Blood Transcriptome Biomarkers Of Admentioning

confidence: 99%

“…In addition to the presence of amyloid plaques in the brain parenchyma and intraneuronal neurofibrillary tangles, emerging evidence suggests the existence of additional AD pathophysiological pathways, such as innate immune responses, neuroinflammation, and vascular and cell membrane dysregulation [3][4][5]. Our previous studies suggest that the detection of transcriptome biomarkers related to cell stress and inflammation in the peripheral blood has significant potential as a minimally invasive and inexpensive diagnostic tool for the diagnosis and early detection of developing AD [6][7][8][9][10][11][12][13][14][15]. Although DNA methylation and RNA expression changes in blood might have utility as biomarkers of cognitive dysfunction and brain aging [16,17], the major limitation of blood biomarkers of AD is the lack of a direct correlation with biomarkers in brain tissues.…”

Section: Introductionmentioning

confidence: 97%

Identifying Blood Transcriptome Biomarkers of Alzheimer’s Disease Using Transgenic Mice

et al. 2020

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The testing of pathological biomarkers of Alzheimer’s disease (AD), such as amyloid beta and tau, is time-consuming, expensive, and invasive. Here, we used 3xTg-AD mice to identify and validate putative novel blood transcriptome biomarkers of AD that can potentially be identified in the blood of patients. mRNA was extracted from the blood and hippocampus of 3xTg-AD and control mice at different ages and used for microarray analysis. Network and functional analyses revealed that the differentially expressed genes between AD and control mice modulated the immune and neuroinflammation systems. Five novel gene transcripts (Cdkn2a, Apobec3, Magi2, Parp3, and Cass4) showed significant increases with age, and their expression in the blood was collated with that in the hippocampus only in AD mice. We further assessed previously identified candidate biomarker genes. The expression of Trem1 and Trem2 in both the blood and brain was significantly increased with age. Decreased Tomm40 and increased Pink1 mRNA levels were observed in the mouse blood. The changes in the expression of Snca and Apoe mRNA in the mouse blood and brain were similar to those found in human AD blood. Our results demonstrated that the immune and neuroinflammatory system is involved in the pathophysiologies of aging and AD and that the blood transcriptome might be useful as a biomarker of AD.

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“…Antigen presentation (Karch and Goate, 2015) rs2301275 PVR NK and T cell function (Stamm et al, 2018a,b) rs2376866 rs117612135 RELB Dendritic cell differentiation, regulation of adaptive immune response (Zanetti et al, 2003) rs190982 MEF2C B cell proliferation and antigen presentation (Sao et al, 2018) Many other SAD associated genes have also been shown to play vital roles in immune reactivity in the brain. Rare variants in TREM2, which are thought to be loss of function, and increase the risk of developing AD by approximately 2-to 4-fold, were identified by whole-genome sequencing (Sierra et al, 2013;Wolf et al, 2017).…”

Section: Epha1mentioning

confidence: 99%

Friend, Foe or Both? Immune Activity in Alzheimer’s Disease

Frost

Jonas

2019

Front. Aging Neurosci.

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Alzheimer's disease (AD) is marked by the presence of amyloid beta (Aβ) plaques, neurofibrillary tangles (NFT), neuronal death and synaptic loss, and inflammation in the brain. AD research has, in large part, been dedicated to the understanding of Aβ and NFT deposition as well as to the pharmacological reduction of these hallmarks. However, recent GWAS data indicates neuroinflammation plays a critical role in AD development, thereby redirecting research efforts toward unveiling the complexities of AD-associated neuroinflammation. It is clear that the innate immune system is intimately associated with AD progression, however, the specific roles of glia and neuroinflammation in AD pathology remain to be described. Moreover, inflammatory processes have largely been painted as detrimental to AD pathology, when in fact, many immune mechanisms such as phagocytosis aid in the reduction of AD pathologies. In this review, we aim to outline the delicate balance between the beneficial and detrimental aspects of immune activation in AD as a more thorough understanding of these processes is critical to development of effective therapeutics for AD.

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MEF2C mRNA expression and cognitive function in Japanese patients with Alzheimer's disease

Abstract: MEF2C mRNA expression in leukocytes may be a biological marker for cognitive decline in AD.

Cited by 39 publications

References 53 publications

Impact of DNA methyltransferase inhibitor 5‐azacytidine on cardiac development of zebrafish in vivo and cardiomyocyte proliferation, apoptosis, and the homeostasis of gene expression in vitro

Impact of DNA methyltransferase inhibitor 5‐azacytidine on cardiac development of zebrafish in vivo and cardiomyocyte proliferation, apoptosis, and the homeostasis of gene expression in vitro

Identifying Blood Transcriptome Biomarkers of Alzheimer’s Disease Using Transgenic Mice

Friend, Foe or Both? Immune Activity in Alzheimer’s Disease

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