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neuronal epigenetics

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https://www.readbyqxmd.com/read/28718992/melatonin-impedes-tet1-dependent-mglur5-promoter-demethylation-to-relieve-pain
#1
Ming-Chun Hsieh, Yu-Cheng Ho, Cheng-Yuan Lai, Dylan Chou, Hsueh-Hsiao Wang, Gin-Den Chen, Tzer-Bin Lin, Hsien-Yu Peng
Melatonin (N-acetyl-5-methoxytryptamine)/MT2 receptor-dependent epigenetic modification represents a novel pathway in the treatment of neuropathic pain. Because spinal ten-eleven translocation methylcytosine dioxygenase 1 (Tet1)-dependent epigenetic demethylation has recently been linked to pain hypersensitivity, we hypothesized that melatonin/MT2-dependent analgesia involves spinal Tet1-dependent demethylation. Here, we showed that spinal Tet1 gene transfer by intrathecal delivery of Tet1-encoding vectors to naïve rats produced profound and long-lasting nociceptive hypersensitivity...
July 18, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28712747/selectivity-and-kinetic-requirements-of-hdac-inhibitors-as-progranulin-enhancers-for-treating-frontotemporal-dementia
#2
Angela She, Iren Kurtser, Surya A Reis, Krista Hennig, Jenny Lai, Audrey Lang, Wen-Ning Zhao, Ralph Mazitschek, Bradford C Dickerson, Joachim Herz, Stephen J Haggarty
Frontotemporal dementia (FTD) arises from neurodegeneration in the frontal, insular, and anterior temporal lobes. Autosomal dominant causes of FTD include heterozygous mutations in the GRN gene causing haploinsufficiency of progranulin (PGRN) protein. Recently, histone deacetylase (HDAC) inhibitors have been identified as enhancers of PGRN expression, although the mechanisms through which GRN is epigenetically regulated remain poorly understood. Using a chemogenomic toolkit, including optoepigenetic probes, we show that inhibition of class I HDACs is sufficient to upregulate PGRN in human neurons, and only inhibitors with apparent fast binding to their target HDAC complexes are capable of enhancing PGRN expression...
July 11, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28710457/methyl-cpg-binding-domain-proteins-inhibit-interspecies-courtship-and-promote-aggression-in-drosophila
#3
Tarun Gupta, Hannah R Morgan, Jonathan C Andrews, Edmond R Brewer, Sarah J Certel
Reproductive isolation and speciation are driven by the convergence of environmental and genetic variation. The integration of these variation sources is thought to occur through epigenetic marks including DNA methylation. Proteins containing a methyl-CpG-binding domain (MBD) bind methylated DNA and interpret epigenetic marks, providing a dynamic yet evolutionarily adapted cellular output. Here, we report the Drosophila MBD-containing proteins, dMBD-R2 and dMBD2/3, contribute to reproductive isolation and survival behavioral strategies...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28700589/ank1-is-up-regulated-in-laser-captured-microglia-in-alzheimer-s-brain-the-importance-of-addressing-cellular-heterogeneity
#4
Diego Mastroeni, Shobana Sekar, Jennifer Nolz, Elaine Delvaux, Katie Lunnon, Jonathan Mill, Winnie S Liang, Paul D Coleman
Recent epigenetic association studies have identified a new gene, ANK1, in the pathogenesis of Alzheimer's disease (AD). Although strong associations were observed, brain homogenates were used to generate the data, introducing complications because of the range of cell types analyzed. In order to address the issue of cellular heterogeneity in homogenate samples we isolated microglial, astrocytes and neurons by laser capture microdissection from CA1 of hippocampus in the same individuals with a clinical and pathological diagnosis of AD and matched control cases...
2017: PloS One
https://www.readbyqxmd.com/read/28698219/the-transcription-factor-c-ebp%C3%AE-in-the-dorsal-root-ganglion-contributes-to-peripheral-nerve-trauma-induced-nociceptive-hypersensitivity
#5
Zhisong Li, Yuanyuan Mao, Lingli Liang, Shaogen Wu, Jingjing Yuan, Kai Mo, Weihua Cai, Qingxiang Mao, Jing Cao, Alex Bekker, Wei Zhang, Yuan-Xiang Tao
Changes in gene transcription in the dorsal root ganglion (DRG) after nerve trauma contribute to the genesis of neuropathic pain. We report that peripheral nerve trauma caused by chronic constriction injury (CCI) increased the abundance of the transcription factor C/EBPβ (CCAAT/enhancer binding protein β) in the DRG. Blocking this increase mitigated the development and maintenance of CCI-induced mechanical, thermal, and cold pain hypersensitivities without affecting basal responses to acute pain and locomotor activity...
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28696319/combined-epigenetic-and-differentiation-based-treatment-inhibits-neuroblastoma-tumor-growth-and-links-hif2%C3%AE-to-tumor-suppression
#6
Isabelle Westerlund, Yao Shi, Konstantinos Toskas, Stuart M Fell, Shuijie Li, Olga Surova, Erik Södersten, Per Kogner, Ulrika Nyman, Susanne Schlisio, Johan Holmberg
Neuroblastoma is a pediatric cancer characterized by variable outcomes ranging from spontaneous regression to life-threatening progression. High-risk neuroblastoma patients receive myeloablative chemotherapy with hematopoietic stem-cell transplant followed by adjuvant retinoid differentiation treatment. However, the overall survival remains low; hence, there is an urgent need for alternative therapeutic approaches. One feature of high-risk neuroblastoma is the high level of DNA methylation of putative tumor suppressors...
July 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28695279/epigenetic-regulation-of-neural-stem-cell-differentiation-towards-spinal-cord-regeneration
#7
REVIEW
Tomonori Kameda, Takuya Imamura, Kinichi Nakashima
Severe spinal cord injury (SCI) leads to almost complete neural cell loss at the injured site, causing the irreversible disruption of neuronal circuits. The transplantation of neural stem or precursor cells (NS/PCs) has been regarded as potentially effective for SCI treatment because NS/PCs can compensate for the injured sites by differentiating into neurons and glial cells (astrocytes and oligodendrocytes). An understanding of the molecular mechanisms that regulate the proliferation, fate specification and maturation of NS/PCs and their progeny would facilitate the establishment of better therapeutic strategies for regeneration after SCI...
July 10, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28694114/epigenetic-dysregulation-of-protocadherins-in-human-disease
#8
REVIEW
Nady El Hajj, Marcus Dittrich, Thomas Haaf
Protocadherins (Pcdhs) are a group of cell-cell adhesion molecules that are highly expressed in the nervous system and have a major function in dendrite development and neural circuit formation. However, the role protocadherins play in human health and disease remains unclear. Several recent studies have associated epigenetic dysregulation of protocadherins with possible implications for disease pathogenesis. In this review, we briefly recap the various epigenetic mechanisms regulating protocadherin genes, particularly the clustered Pcdhs...
July 7, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28691768/microbiome-inflammation-epigenetic-alterations-and-mental-diseases
#9
REVIEW
Reza Alam, Hamid M Abdolmaleky, Jin-Rong Zhou
Major mental diseases such as autism, bipolar disorder, schizophrenia, and major depressive disorder are debilitating illnesses with complex etiologies. Recent findings show that the onset and development of these illnesses cannot be well described by the one-gene; one-disease approach. Instead, their clinical presentation is thought to result from the regulative interplay of a large number of genes. Even though the involvement of many genes are likely, up regulating and activation or down regulation and silencing of these genes by the environmental factors play a crucial role in contributing to their pathogenesis...
July 10, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28685029/does-gastric-bypass-surgery-change-body-weight-set-point
#10
REVIEW
Z Hao, M B Mumphrey, C D Morrison, H Münzberg, J Ye, H R Berthoud
The relatively stable body weight during adulthood is attributed to a homeostatic regulatory mechanism residing in the brain which uses feedback from the body to control energy intake and expenditure. This mechanism guarantees that if perturbed up or down by design, body weight will return to pre-perturbation levels, defined as the defended level or set point. The fact that weight re-gain is common after dieting suggests that obese subjects defend a higher level of body weight. Thus, the set point for body weight is flexible and likely determined by the complex interaction of genetic, epigenetic and environmental factors...
December 2016: International Journal of Obesity Supplements
https://www.readbyqxmd.com/read/28682229/-epigenetic-mechanisms-and-alcohol-use-disorders-a-potential-therapeutic-target
#11
Rémi Legastelois, Jérôme Jeanblanc, Catherine Vilpoux, Erika Bourguet, Mickael Naassila
Alcohol use disorder is a devastating illness with a profound health impact, and its development is dependent on both genetic and environmental factors. This disease occurs over time and requires changes in brain gene expression. There is converging evidence suggesting that the epigenetic processes may play a role in the alcohol-induced gene regulations and behavior such as the intervention of DNA methylation and histone acetylation. Histone acetylation, like histone methylation, is a highly dynamic process regulated by two classes of enzymes: histone acetyltransferases and histone deacetylases (HDACs)...
2017: Biologie Aujourd'hui
https://www.readbyqxmd.com/read/28665013/epigenetic-regulation-by-g9a-glp-complex-ameliorates-amyloid-beta-1-42-induced-deficits-in-long-term-plasticity-and-synaptic-tagging-capture-in-hippocampal-pyramidal-neurons
#12
Mahima Sharma, Tobias Dierkes, Sreedharan Sajikumar
Altered epigenetic mechanisms are implicated in the cognitive decline associated with neurodegenerative diseases such as in Alzheimer's disease (AD). AD is the most prevalent form of dementia worldwide; amyloid plaques and neurofibrillary tangles are the histopathological hallmarks of AD. We have recently reported that the inhibition of G9a/GLP complex promotes long-term potentiation (LTP) and its associative mechanisms such as synaptic tagging and capture (STC). However, the role of this complex in plasticity impairments remains elusive...
June 30, 2017: Aging Cell
https://www.readbyqxmd.com/read/28664454/microrna-directed-neuronal-reprogramming-as-a-therapeutic-strategy-for-neurological-diseases
#13
REVIEW
Irene Faravelli, Stefania Corti
The loss of neurons due to injury and disease results in a wide spectrum of highly disabling neurological and neurodegenerative conditions, given the apparent limited capacity of endogenous repair of the adult central nervous system (CNS). Therefore, it is important to develop technologies that can promote de novo neural stem cell and neuron generation. Current insights in CNS development and cellular reprogramming have provided the knowledge to finely modulate lineage-restricted transcription factors and microRNAs (miRNA) to elicit correct neurogenesis...
June 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28662822/matrix-metalloproteinases-neural-extracellular-matrix-and-central-nervous-system-pathology
#14
Ciro De Luca, Michele Papa
The functionality and stability of the central nervous system (CNS) pabulum, called neural extracellular matrix (nECM), is paramount for the maintenance of a healthy network. The loosening or the damage of the scaffold disrupts synaptic transmission with the consequent imbalance of the neurotransmitters, reactive cells invasion, astrocytosis, new matrix deposition, digestion of the previous structure and ultimately, maladaptive plasticity with the loss of neuronal viability. nECM is constantly affected by CNS disorders, particularly in chronic modifying such as neurodegenerative disease, or in acute/subacute with chronic sequelae, like cerebrovascular and inflammatory pathology...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28648897/unique-organization-of-the-nuclear-envelope-in-the-post-natal-quiescent-neural-stem-cells
#15
Arantxa Cebrián-Silla, Clara Alfaro-Cervelló, Vicente Herranz-Pérez, Naoko Kaneko, Dae Hwi Park, Kazunobu Sawamoto, Arturo Alvarez-Buylla, Daniel A Lim, José Manuel García-Verdugo
Neural stem cells (B1 astrocytes; NSCs) in the adult ventricular-subventricular-zone (V-SVZ) originate in the embryo. Surprisingly, recent work has shown that B1 cells remain largely quiescent. They are reactivated postnatally to function as primary progenitors for neurons destined for the olfactory bulb and some corpus callosum oligodendrocytes. The cellular and molecular properties of quiescent B1 cells remain unknown. Here we found that a subpopulation of B1 cells has a unique nuclear envelope invagination specialization similar to envelope-limited chromatin sheets (ELCS), reported in certain lymphocytes and some cancer cells...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28648366/-oxidative-stress-in-perinatal-asphyxia-and-hypoxic-ischaemic-encephalopathy
#16
Antonio Nuñez, Isabel Benavente, Dorotea Blanco, Héctor Boix, Fernando Cabañas, Mercedes Chaffanel, Belén Fernández-Colomer, José Ramón Fernández-Lorenzo, Begoña Loureiro, María Teresa Moral, Antonio Pavón, Inés Tofé, Eva Valverde, Máximo Vento
Birth asphyxia is one of the principal causes of early neonatal death. In survivors it may evolve to hypoxic-ischaemic encephalopathy and major long-term neurological morbidity. Prolonged and intense asphyxia will lead to energy exhaustion in tissues exclusively dependent on aerobic metabolism, such as the central nervous system. Energy deficit leads to ATP-dependent pumps blockage, with the subsequent loss of neuronal transmembrane potential. The most sensitive areas of the brain will die due to necrosis. In more resistant areas, neuronal hyper-excitability, massive entrance of ionic calcium, activation of NO-synthase, free radical generation, and alteration in mitochondrial metabolism will lead to a secondary energy failure and programmed neuronal death by means of the activation of the caspase pathways...
June 22, 2017: Anales de Pediatría: Publicación Oficial de la Asociación Española de Pediatría (A.E.P.)
https://www.readbyqxmd.com/read/28644712/comparative-analysis-of-behavioral-and-transcriptional-variation-underlying-co2-sensory-neuron-function-and-development-in-drosophila
#17
Jia Wern Pan, Joi McLaughlin, Haining Yang, Charles Leo, Paula Rambarat, Sumie Okuwa, Anaïs Monroy-Eklund, Sabrina Clark, Corbin D Jones, Pelin Cayirlioglu Volkan
Carbon dioxide is an important environmental cue for many insects, regulating many behaviors including some that have direct human impacts. To further improve our understanding of how this system varies among closely related insect species, we examined both the behavioral response to CO2 as well as the transcriptional profile of key developmental regulators of CO2 sensory neurons in the olfactory system across the Drosophila genus. We found that CO2 generally evokes repulsive behavior across most of the Drosophilids we examined, but this behavior has been lost or reduced in several lineages...
June 23, 2017: Fly
https://www.readbyqxmd.com/read/28635037/novel-role-and-regulation-of-hdac4-in-cocaine-related-behaviors
#18
Rachel D Penrod, Maria B Carreira, Makoto Taniguchi, Jaswinder Kumar, Stephanie A Maddox, Christopher W Cowan
Epigenetic mechanisms have been proposed to contribute to persistent aspects of addiction-related behaviors. One family of epigenetic molecules that may regulate maladaptive behavioral changes produced by cocaine use are the histone deacetylases (HDACs)-key regulators of chromatin and gene expression. In particular, the class IIa HDACs (HDAC4, HDAC5, HDAC7 and HDAC9) respond to changes in neuronal activity by modulating their distribution between the nucleus and cytoplasm-a process controlled in large part by changes in phosphorylation of conserved residues...
June 21, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28634230/similarity-in-gene-regulatory-networks-suggests-that-cancer-cells-share-characteristics-of-embryonic-neural-cells
#19
Zan Zhang, Anhua Lei, Liyang Xu, Lu Chen, Yonglong Chen, Xuena Zhang, Yan Gao, Xiaoli Yang, Min Zhang, Ying Cao
Cancer cells are immature cells resulting from cellular reprogramming by gene misregulation, and re-differentiation is expected to reduce malignancy. It is unclear, however, whether cancer cells can undergo terminal differentiation. Here, we show that, inhibition of the epigenetic modification enzymes enhancer of zeste homolog 2 (EZH2), histone deacetylases (HDACs) 1 and 3, lysine demethylase 1A (LSD1), or DNA methyltransferase 1 (DNMT1), which all promote cancer development and progression, leads to postmitotic neuron-like differentiation with loss of malignant features in distinct solid cancer cell lines...
June 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28628196/molecular-mechanisms-of-experience-dependent-maturation-in-cortical-gabaergic-inhibition
#20
REVIEW
M Ridzwana Begum, Judy C G Sng
Critical periods (CP) in early postnatal life are periods of plasticity during which the neuronal circuitry is most receptive to environmental stimuli. These early experiences translate to a more permanent and sophisticated neuronal connection in the adult brain systems. Multiple studies have pointed to the development of inhibitory circuitry as one of the central factors for the onset of critical periods. We discuss several molecular mechanisms regulating inhibitory circuit maturation and CP, from gene transcription level to protein signaling level...
June 19, 2017: Journal of Neurochemistry
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