Neurocalcin Delta Knockout Impairs Adult Neurogenesis Whereas Half Reduction Is Not Pathological

Upadhyay, Aaradhita; Hosseinibarkooie, Seyyedmohsen; Schneider, Svenja; Kaczmarek, Anna; Torres-Benito, Laura; Mendoza-Ferreira, Natalia; Overhoff, Melina; Rombo, Roman; Grysko, Vanessa; Kye, Min Jeong; Kononenko, Natalia L.; Wirth, Brunhilde

doi:10.3389/fnmol.2019.00019

Cited by 27 publications

(28 citation statements)

References 61 publications

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“…In AD, the GABA signaling system is dysregulated with changes in GABA expression in the hippocampus (Calvo-Flores Guzmán et al, 2018). NCALD is a calcium sensor that is involved in neuronal calcium signaling (Stelzer et al, 2016; Upadhyay et al, 2019). NEFL makes the protein neurofilament light chain (Nfl), which has recently been investigated as a fluid biomarker for monitoring AD disease progression (Preische et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Data-Driven Analysis of Age, Sex, and Tissue Effects on Gene Expression Variability in Alzheimer's Disease

Brooks

Mias

2019

Front. Neurosci.

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Alzheimer's disease (AD) has been categorized by the Centers for Disease Control and Prevention (CDC) as the 6 th leading cause of death in the United States. AD is a significant health-care burden because of its increased occurrence (specifically in the elderly population), and the lack of effective treatments and preventive methods. With an increase in life expectancy, the CDC expects AD cases to rise to 15 million by 2060. Aging has been previously associated with susceptibility to AD, and there are ongoing efforts to effectively differentiate between normal and AD age-related brain degeneration and memory loss. AD targets neuronal function and can cause neuronal loss due to the buildup of amyloid-beta plaques and intracellular neurofibrillary tangles. Our study aims to identify temporal changes within gene expression profiles of healthy controls and AD subjects. We conducted a meta-analysis using publicly available microarray expression data from AD and healthy cohorts. For our meta-analysis, we selected datasets that reported donor age and gender, and used Affymetrix and Illumina microarray platforms (8 datasets, 2,088 samples). Raw microarray expression data were re-analyzed, and normalized across arrays. We then performed an analysis of variance, using a linear model that incorporated age, tissue type, sex, and disease state as effects, as well as study to account for batch effects, and included binary interactions between factors. Our results identified 3,735 statistically significant (Bonferroni adjusted p < 0.05) gene expression differences between AD and healthy controls, which we filtered for biological effect (10% two-tailed quantiles of mean differences between groups) to obtain 352 genes. Interesting pathways identified as enriched comprised of neurodegenerative diseases pathways (including AD), and also mitochondrial translation and dysfunction, synaptic vesicle cycle and GABAergic synapse, and gene ontology terms enrichment in neuronal system, transmission across chemical synapses and mitochondrial translation. Overall our approach allowed us to effectively combine multiple available microarray datasets and identify gene expression differences between AD and healthy individuals including full age and tissue type considerations. Our findings provide potential gene and pathway associations that can be targeted to improve AD diagnostics and potentially treatment or prevention.

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Section: Discussionmentioning

confidence: 99%

Data-Driven Analysis of Age, Sex, and Tissue Effects on Gene Expression Variability in Alzheimer's Disease

Brooks

Mias

2019

Front. Neurosci.

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“…Overexpressed Ncald induced a reduction in axon outgrowth and branching of cultured hippocampal neurons ( Yamatani et al ., 2010 ), and Ncald KO restored axonal growth in zebrafish and mice ( Riessland et al ., 2017 ). In contrast, Upadhyay et al . (2019) reported that Ncald KO impaired neurogenesis in adult mice, while Ncald heterozygous mice did not exhibit significant changes.…”

Section: Discussionmentioning

confidence: 84%

Gene Expression Profiling in the Striatum of Per2 KO Mice Exhibiting More Vulnerable Responses against Methamphetamine

Kim

Jeon

Custodio

et al. 2021

Biomolecules & Therapeutics

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Drug addiction influences most communities directly or indirectly. Increasing studies have reported the relationship between circadian-related genes and drug addiction. Per2 disrupted mice exhibited more vulnerable behavioral responses against some drugs including methamphetamine (METH). However, its roles and mechanisms are still not clear. Transcriptional profiling analysis in Per2 knockout (KO) mice may provide a valuable tool to identify potential genetic involvement and pathways in enhanced behavioral responses against drugs. To explore the potential genetic involvement, we examined common differentially expressed genes (DEGs) in the striatum of drug naïve Per2 KO/wild-type (WT) mice, and before/after METH treatment in Per2 KO mice, but not in WT mice. We selected 9 common DEGs ( Ncald , Cpa6 , Pklr , Ttc29 , Cbr2 , Egr2 , Prg4 , Lcn2 , and Camsap2 ) based on literature research. Among the common DEGs, Ncald , Cpa6 , Pklr , and Ttc29 showed higher expression levels in drug naïve Per2 KO mice than in WT mice, while they were downregulated in Per2 KO mice after METH treatment. In contrast, Cbr2 , Egr2 , Prg4 , Lcn2 , and Camsap2 exhibited lower expression levels in drug naïve Per2 KO mice than in WT mice, while they were upregulated after METH treatment in Per2 KO mice. qRT-PCR analyses validated the expression patterns of 9 target genes before/after METH treatment in Per2 KO and WT mice. Although further research is required to deeply understand the relationship and roles of the 9 target genes in drug addiction, the findings from the present study indicate that the target genes might play important roles in drug addiction.

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“…NCALD, AT2A2 (also known as SERCA2) and AT2B1 are play pivotal role in the calcium homeostasis. NCALD primarily involved in neuronal calcium signaling mechanism and it is speculated that there is a close relationship between NCAL and adult neurogenesis [23]. SERCA2 is an intracellular calcium pump on the endoplasmic or sarcoplasmic reticulum, plays an essential role in regulating calcium homeostasis [24,25].…”

Section: Discussionmentioning

confidence: 99%

The role of circadian rhythm in the regulation of cellular protein profiles in the brain

Beker¹,

Kılıç²

2021

Turk J Med Sci

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Background/aim: Circadian rhythm plays a significant role in the regulation of almost all kinds of physiological processes. Besides this it may also have a direct or indirect effect on the neurodegenerative processes, including Alzheimer's disease, Parkinson's disease, and ischemic stroke. Therefore, the identification of circadian rhythm related proteins is crucial to be able to understand the molecular mechanism of the circadian rhythm and to define new therapeutic target for the treatment of degenerative disorders. Materials and methods: To identify the light and dark regulated proteins, 8-12 weeks, male Balb/C mice were used at two different time points (Morning (Zeitgeber time-0 (ZT0)) and midnight (ZT18)) under physiological conditions. Therefore, brain tissues were analyzed via liquid chromatography tandem-mass spectrometry. Results: A totally of 1621 different proteins were identified between ZT0 and ZT18 mice. Among these proteins, 23 proteins were differentially expressed (p<0.05 and fold change 1.4) in ZT18 mice, 11 upregulated (AKAP10,

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Neurocalcin Delta Knockout Impairs Adult Neurogenesis Whereas Half Reduction Is Not Pathological

Cited by 27 publications

References 61 publications

Data-Driven Analysis of Age, Sex, and Tissue Effects on Gene Expression Variability in Alzheimer's Disease

Data-Driven Analysis of Age, Sex, and Tissue Effects on Gene Expression Variability in Alzheimer's Disease

Gene Expression Profiling in the Striatum of Per2 KO Mice Exhibiting More Vulnerable Responses against Methamphetamine

The role of circadian rhythm in the regulation of cellular protein profiles in the brain

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