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neuronal epigenetics

S Obernikhin, N Yaglova, D Tsomartova, V Torbek, M Ivanova
Chromaffin cells of adrenal medulla have traditionally been considered as modified sympathetic neurons. However, the results of recent studies indicate the need to revise this concept. The article reviews recent findings in origin and ontogeny of adrenal chromaffin cells and transcriptional and posttranscriptional regulation of developmental processes. The article summarizes data on transcriptional control of chromaffin cells proliferation and maturation and participation of microRNA in regulation of chromaffin and sympathetic neuronal phenotype gene expression...
May 2018: Georgian Medical News
Soneela Ankam, Benjamin K K Teo, Grace Pohan, Shawn W L Ho, Choon K Lim, Evelyn K F Yim
Stem cell differentiation can be regulated by biophysical cues such as nanotopography. It involves sensing and integration of these biophysical cues into their transcriptome with a mechanism that is yet to be discovered. In addition to the cytoskeletal and focal adhesion remodeling, nanotopography has also been shown to modulate nucleus morphology. Here, we studied the effect of nanotopography on the temporal changes in nuclei of human embryonic stem cells (hESCs) and human mesenchymal stem cells (hMSCs). Using a high throughput Multi-architecture (MARC) chip analysis, the circularity of the stem cell nuclei changed significantly on different patterns...
2018: Frontiers in Bioengineering and Biotechnology
Francesco Rusconi, Elena Battaglioli
Psychiatric disorders entail maladaptive processes impairing individuals' ability to appropriately interface with environment. Among them, depression is characterized by diverse debilitating symptoms including hopelessness and anhedonia, dramatically impacting the propensity to live a social and active life and seriously affecting working capability. Relevantly, besides genetic predisposition, foremost risk factors are stress-related, such as experiencing chronic psychosocial stress-including bullying, mobbing and abuse-, and undergoing economic crisis or chronic illnesses...
2018: Frontiers in Molecular Neuroscience
Maria E Ramirez-Roman, Carlos E Billini, Alfredo Ghezzi
Alcohol addiction is a serious condition perpetuated by enduring physiological and behavioral adaptations. An important component of these adaptations is the long-term rearrangement of neuronal gene expression in the brain of the addicted individual. Epigenetic histone modifications have recently surfaced as important modulators of the transcriptional adaptation to alcohol as these are thought to represent a form of transcriptional memory that is directly imprinted on the chromosome. Some histone modifications affect transcription by modulating the accessibility of the underlying DNA, whereas others have been proposed to serve as marks read by transcription factors as a "histone code" that helps to specify the expression level of a gene...
2018: Journal of Experimental Neuroscience
Chuan Xu, Qian Li, Olga Efimova, Liu He, Shoji Tatsumoto, Vita Stepanova, Takao Oishi, Toshifumi Udono, Katsushi Yamaguchi, Shuji Shigenobu, Akiyoshi Kakita, Hiroyuki Nawa, Philipp Khaitovich, Yasuhiro Go
Molecular maps of the human brain alone do not inform us of the features unique to humans. Yet, the identification of these features is important for understanding both the evolution and nature of human cognition. Here, we approached this question by analyzing gene expression and H3K27ac chromatin modification data collected in eight brain regions of humans, chimpanzees, gorillas, a gibbon and macaques. An analysis of spatial transcriptome trajectories across eight brain regions in four primate species revealed 1,851 genes showing human-specific transcriptome differences in one or multiple brain regions, in contrast to 240 chimpanzee-specific ones...
June 13, 2018: Genome Research
Mareike Albert, Wieland B Huttner
Neurogenesis is the process through which neural stem and progenitor cells generate neurons. During the development of the mouse neocortex, stem and progenitor cells sequentially give rise to neurons destined to different cortical layers and then switch to gliogenesis resulting in the generation of astrocytes and oligodendrocytes. Precise spatial and temporal regulation of neural progenitor differentiation is key for the proper formation of the complex structure of the neocortex. Dynamic changes in gene expression underlie the coordinated differentiation program, which enables the cells to generate the RNAs and proteins required at different stages of neurogenesis and across different cell types...
2018: Frontiers in Neuroscience
Dan Zhu, Satoru Osuka, Zhaobin Zhang, Zachery R Reichert, Liquan Yang, Yonehiro Kanemura, Ying Jiang, Shuo You, Hanwen Zhang, Narra S Devi, Debanjan Bhattacharya, Shingo Takano, G Yancey Gillespie, Tobey Macdonald, Chalet Tan, Ryo Nishikawa, William G Nelson, Jeffrey J Olson, Erwin G Van Meir
Adhesion G protein-coupled receptors (ADGRs) encompass 33 human transmembrane proteins with long N termini involved in cell-cell and cell-matrix interactions. We show the ADGRB1 gene, which encodes Brain-specific angiogenesis inhibitor 1 (BAI1), is epigenetically silenced in medulloblastomas (MBs) through a methyl-CpG binding protein MBD2-dependent mechanism. Knockout of Adgrb1 in mice augments proliferation of cerebellar granule neuron precursors, and leads to accelerated tumor growth in the Ptch1+/- transgenic MB mouse model...
June 11, 2018: Cancer Cell
Jonathan J Sabbagh, Ricardo A Cordova, Dali Zheng, Marangelie Criado-Marrero, Andrea Lemus, Pengfei Li, Jeremy D Baker, Bryce A Nordhues, April L Darling, Carlos Martinez-Licha, Daniel A Rutz, Shreya Patel, Johannes Buchner, James W Leahy, John Koren, Chad A Dickey, Laura J Blair
Genetic and epigenetic alterations in FK506-binding protein 5 (FKBP5) have been associated with increased risk for psychiatric disorders, including post-traumatic stress disorder (PTSD). These variants can increase the expression of FKBP5, the gene that encodes FKBP51. Excess FKBP51 promotes hypothalamic-pituitary-adrenal (HPA) axis dysregulation through altered glucocorticoid receptor (GR) signaling. Thus, we hypothesized that GR activity could be restored by perturbing FKBP51. Here, we report that depletion of FKBP51 from the GR/90kDa heat shock protein (Hsp90) complex increased GR signaling in vivo...
June 12, 2018: ACS Chemical Biology
Yanchun Pan, Ying Zhu, Wei Yang, Eric Tycksen, Shaopeng Liu, John Palucki, Linjian Zhu, Yo Sasaki, Mukesh K Sharma, Albert H Kim, Bo Zhang, Hiroko Yano
Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an abnormal expansion of polyglutamine repeats in the huntingtin protein (Htt). Transcriptional dysregulation is an early event in the course of HD progression and is thought to contribute to disease pathogenesis. But how mutant Htt causes transcriptional alterations and subsequent cell death in neurons is not well understood. RNA-sequencing analysis revealed that expression of a mutant Htt fragment in primary cortical neurons leads to robust gene expression changes before neuronal death...
June 11, 2018: Journal of Biological Chemistry
Amit Berson, Raffaella Nativio, Shelley L Berger, Nancy M Bonini
Mechanisms of epigenetic regulation, including DNA methylation, chromatin remodeling, and histone post-translational modifications, are involved in multiple aspects of neuronal function and development. Recent discoveries have shed light on critical functions of chromatin in the aging brain, with an emerging realization that the maintenance of a healthy brain relies heavily on epigenetic mechanisms. Here, we present recent advances, with a focus on histone modifications and the implications for several neurodegenerative diseases including Alzheimer's disease (AD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS)...
June 6, 2018: Trends in Neurosciences
Artur G Leme Silva, Maíra H Nagai, Bettina Malnic
The mouse olfactory epithelium is composed of a heterogeneous population of olfactory sensory neurons, where each neuron expresses one single type of odorant receptor gene, out of a repertoire of ~1000 different genes. Fluorescent-activated cell sorting (FACS) is a powerful technique, which can be used to isolate a cellular subpopulation from a heterogeneous tissue. The sorted neurons can then be used in gene expression studies, or analyzed for the presence of different DNA epigenetic modification marks. Here we describe a method to separate a subpopulation of olfactory sensory neurons expressing the odorant receptor Olfr17...
2018: Methods in Molecular Biology
Toshiki Aiba, Toshiyuki Saito, Akiko Hayashi, Shinji Sato, Harunobu Yunokawa, Toru Maruyama, Wataru Fujibuchi, Seiichiroh Ohsako
Background: There is still considerable debate about the effects of exposure to bisphenol A (BPA) an endocrine disrupter at low doses. Recently, many studies using animal models have shown that prenatal BPA exposure induces behavioral and neuronal disorders due to epigenetic changes in the brain. However, striking evidence of epigenomic changes has to be shown. Methods: To investigate whether low-dose BPA exposure in the fetal stage can alter CpG methylation levels in the central nervous system, the hippocampus of the inbred C57BL/6 J mouse as the target tissue was collected to detect alterations in CpG methylation levels using a highly sensitive method of genome-wide DNA methylation analysis, methylated site display-amplified fragment length polymorphism (MSD-AFLP)...
2018: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
Kui Xie, Allan Sheppard
The metabolic requirements of differentiated neurons are significantly different from that of neuronal precursor and neural stem cells. While a re-programming of metabolism is tightly coupled to the neuronal differentiation process, whether shifts in mitochondrial mass, glycolysis, and oxidative phosphorylation are required (or merely consequential) in differentiation is not yet certain. In addition to providing more energy, enhanced metabolism facilitates differentiation by supporting increased neurotransmitter signaling and underpinning epigenetic regulation of gene expression...
June 7, 2018: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
Gonca Bayraktar, Michael R Kreutz
Over the last decade, an increasing number of reports underscored the importance of epigenetic regulations in brain plasticity. Epigenetic elements such as readers, writers and erasers recognize, establish, and remove the epigenetic tags in nucleosomes, respectively. One such regulation concerns DNA-methylation and demethylation, which are highly dynamic and activity-dependent processes even in the adult neurons. It is nowadays widely believed that external stimuli control the methylation marks on the DNA and that such processes serve transcriptional regulation in neurons...
2018: Frontiers in Molecular Neuroscience
Rocco Piazza, Vera Magistroni, Sara Redaelli, Mario Mauri, Luca Massimino, Alessandro Sessa, Marco Peronaci, Maciej Lalowski, Rabah Soliymani, Caterina Mezzatesta, Alessandra Pirola, Federica Banfi, Alicia Rubio, Delphine Rea, Fabio Stagno, Emilio Usala, Bruno Martino, Leonardo Campiotti, Michele Merli, Francesco Passamonti, Francesco Onida, Alessandro Morotti, Francesca Pavesi, Marco Bregni, Vania Broccoli, Marc Baumann, Carlo Gambacorti-Passerini
SETBP1 variants occur as somatic mutations in several hematological malignancies such as atypical chronic myeloid leukemia and as de novo germline mutations in the Schinzel-Giedion syndrome. Here we show that SETBP1 binds to gDNA in AT-rich promoter regions, causing activation of gene expression through recruitment of a HCF1/KMT2A/PHF8 epigenetic complex. Deletion of two AT-hooks abrogates the binding of SETBP1 to gDNA and impairs target gene upregulation. Genes controlled by SETBP1 such as MECOM are significantly upregulated in leukemias containing SETBP1 mutations...
June 6, 2018: Nature Communications
Judit Garriga, Geoffroy Laumet, Shao-Rui Chen, Yuhao Zhang, Jozef Madzo, Jean-Pierre J Issa, Hui-Lin Pan, Jaroslav Jelinek
Nerve injury-induced hyperactivity of primary sensory neurons in the dorsal root ganglion (DRG) contributes to chronic pain development, but the underlying epigenetic mechanisms remain poorly understood. Here we determined genome-wide changes in DNA methylation in the nervous system in neuropathic pain. Spinal nerve ligation (SNL), but not paclitaxel treatment, in male Sprague-Dawley rats induced a consistent low-level hypomethylation in the CpG sites in the DRG during the acute and chronic phase of neuropathic pain...
June 6, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Marc Muschler, Mathias Rhein, Andreas Ritter, Thomas Hillemacher, Helge Frieling, Stefan Bleich, Alexander Glahn
Impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis is substantially involved in several psychiatric disorders. Smoking interferes with HPA axis by activating proopiomelanocortin (POMC) neurons and thus stimulating the expression of POMC. The POMC transcript is processed into several peptide hormones, such as adrenocorticotropic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH), that play a role in stress response and weight control. In alcohol dependence, POMC promoter methylation is associated with craving...
June 2, 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Francesca Luisa Conforti, Rosanna Tortelli, Giovanna Morello, Rosa Capozzo, Maria Rosaria Barulli, Sebastiano Cavallaro, Giancarlo Logroscino
The objective of the study was to present a detailed clinical, genetic, and epigenetic characterization of 2 amyotrophic lateral sclerosis (ALS) concordant dizygotic twins. The described cases underwent clinical and paraclinical examinations according to the motor neuron disease protocol of our referral center. Mutation analysis of the major causative genes related to ALS was performed. The methylation profile of the CpG island located in the promoter region of C9orf72 and in the repeat region itself was investigated by bisulfite sequencing of C9orf72 expansion carriers...
June 1, 2018: Neurobiology of Aging
M C Gerra, C Dagostino, S D'Agnelli, L Boggiani, V Rizza, M Marchesini, M Allegri, G Fanelli
Aims The present study aims to identify the underlying mechanisms in the acute to chronic pain transition. Acute pain is a physiological response to an experience of noxious stimuli that can progress to chronic, becoming a disease. The negative consequences as personal suffering, reduction in physical function, maladaptive behaviours, reduction of productivity, make this condition a central and common problem affecting individuals and the society. After an acute damage, pain in some cases persists, being the process attributed to different causes, in particular persistent tissue and neuronal damages, central neuroplastic changes, psychosocial factors...
December 29, 2017: Scandinavian Journal of Pain
Albert Stuart Reece, Wei Wang, Gary Kenneth Hulse
The recent demonstration that addiction-relevant neuronal ensembles defined by known master transcription factors and their connectome is networked throughout mesocorticolimbic reward circuits and resonates harmonically at known frequencies implies that single-cell pan-omics techniques can improve our understanding of Substance Use Disorders (SUD's). Application of machine learning algorithms to such data could find diagnostic utility as biomarkers both to define the presence of the disorder and to quantitate its severity and find myriad applications in a developmental pipeline towards therapeutics and cure...
July 2018: Medical Hypotheses
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