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Objective @#To investigate the expression differences of helix⁃loop⁃helix hand domain family member D 1/2(EFhd1/2) in Alzheimer′s disease (AD) patients and model mice.@*Methods @#The expression changes of EFhd1/2 in AD patients were compared by using data from Alzheimer′s disease database (AlzData), and the changes in mRNA levels and protein levels of EFhd1/2 in brain tissues of AD patients and healthy control group were detected by qPCR and Western blot. The changes of EFhd1/2 mRNA and protein expression in brain tissues of AD models and wild⁃type mice of 3⁃month⁃old and 6⁃month⁃old were detected. Microglia were isolated from AD models and detected the changes of EFhd1/2 by RNA⁃sequencing.@*Results @#The Analysis of Alzheimer′s Disease Database data showed that the mRNA levels of EFhd1 in AD patients increased, while EFhd2 decreased. AD patients brain tissue samples showed an upward trend in the expression of EFhd1 in different brain regions of AD patients compared with healthy controls, while EFhd2 was not different. In the AD mice model, the mRNA levels of EFhd1 were similar in both 3⁃month⁃old and 6⁃month⁃old AD mice compared with wild⁃type mice, but the protein levels of EFhd1 increased; the mRNA levels of EFhd2 increased in 3⁃month⁃old AD mice, and protein levels remained similar in the brain tissue from AD mice aged 3 months and 6 months. However, EFhd2 increased in microglia from 6⁃month old AD mice.@*Conclusion @#EFhd1 increased in both AD model mice and brain tissue of AD patients, suggesting that EFhd1 might play an important role in the development of AD, while EFhd2 increased in microglia in AD model mice, indicating that EFhd2 might be involved in AD related microglia activation and neuroinflammation.

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Astrocytes are an abundant subgroup of cells in the central nervous system (CNS) that play a critical role in controlling neuronal circuits involved in emotion, learning, and memory. In clinical cases, multiple chronic brain diseases may cause psychosocial and cognitive impairment, such as depression and Alzheimer's disease (AD). For years, complex pathological conditions driven by depression and AD have been widely perceived to contribute to a high risk of disability, resulting in gradual loss of self-care ability, lower life qualities, and vast burden on human society. Interestingly, correlational research on depression and AD has shown that depression might be a prodrome of progressive degenerative neurological disease. As a kind of multifunctional glial cell in the CNS, astrocytes maintain physiological function via supporting neuronal cells, modulating pathologic niche, and regulating energy metabolism. Mounting evidence has shown that astrocytic dysfunction is involved in the progression of depression and AD. We herein review the current findings on the roles and mechanisms of astrocytes in the development of depression and AD, with an implication of potential therapeutic avenue for these diseases by targeting astrocytes.

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Microglia-mediated neuroinflammation is widely perceived as a contributor to numerous neurological diseases and mental disorders including depression. Discs large homolog 1 (Dlg1), an adaptor protein, regulates cell polarization and the function of K

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Microglia-mediated neuroinflammation is widely perceived as a contributor to numerous neurological diseases and mental disorders including depression. Discs large homolog 1 (Dlg1), an adaptor protein, regulates cell polarization and the function of K

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Mitochondrial calcium uniporter (MCU) is a conserved Ca(2+) transporter at mitochondrial in eukaryotic cells. However, the role of MCU protein in oxidative stress-induced cell death remains unclear. Here, we showed that ectopically expressed MCU is mitochondrial localized in both HeLa and primary cerebellar granule neurons (CGNs). Knockdown of endogenous MCU decreases mitochondrial Ca(2+) uptake following histamine stimulation and attenuates cell death induced by oxidative stress in both HeLa cells and CGNs. We also found MCU interacts with VDAC1 and mediates VDAC1 overexpression-induced cell death in CGNs. This finding demonstrates that MCU-VDAC1 complex regulates mitochondrial Ca(2+) uptake and oxidative stress-induced apoptosis, which might represent therapeutic targets for oxidative stress related diseases.

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Alzheimer's disease (AD) is the most common neurodegenerative disease among elderly people worldwide. Several genes have been validated to be associated with AD, and calcium homeostasis modulator 1 (Calhm1) is the latest suspected one. To investigate the biological and pathological function of Calhm1 systematically, we generated a Calhm1 conventional knockout mouse. However, both the male and female of elderly Calhm1 knockout (KO) mice showed similar ability to their wild type littermates in spatial learning and memory retrieving. Surprisingly, we found that Calhm1 mRNA could not be detected in mouse brains at different ages, although it is expressed in the human brain tissues. We further found that CpG islands (CGIs) of both mouse and human Calhm1 were hypermethylated, whereas CGI of mouse Calhm2 was hypomethylated. In addition, transcriptional active marker H3K4Di occupied on promoters of human Calhm1 and mouse Calhm2 at a considerable level in brain tissues, while the occupancy of H3K4Di on promoter of mouse Calhm1 was rare. In sum, we found that mouse Calhm1 was of rare abundance in brain tissues. So it might not be suitable to utilize the knockout murine model to explore biological function of Calhm1 in the pathogenesis of AD.

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