scholarly journals Histone Glutamine Modification by Neurotransmitters: Paradigm Shift in the Epigenetics of Neuronal Gene Activation and Dopaminergic VTA Reward Pathway

2020 ◽  
Author(s):  
Samir PATRA
Keyword(s):  
Gene Expression ◽  
Neuronal Development ◽  
Tissue Transglutaminase ◽  
Gene Activation ◽  
Central Element ◽  
Dopamine Neurons ◽  
Normal Brain ◽  
Reward Pathway ◽  
Neuronal Functions ◽  
The Brain

Normal brain function means fine-tuned neuronal circuitry with optimum neurotransmitter signaling. The classical views and experimental demonstrations established neurotransmitters release-uptake through synaptic vesicles. Current research highlighted that neurotransmitters not merely influence electrical impulses; however, contribute to gene expression, now we know, by posttranslational modifications of chromatinised histones. Epigenetic modifications of chromatin, like DNA methylation, histone methylation, acetylation, ubiquitilation etc., influence gene expression during neuronal development, differentiation and functions. Protein glutamine (Q) modification by tissue transglutaminase (TGM2) controls a wide array of metabolic and signaling activities, including neuronal functions. Dopamine neurons are central element in the brain reward system that controls the learning of numerous behaviours. The ventral tegmental area (VTA) consists of dopamine, GABA, or glutamate neurons. The VTA and adjacent substantia nigra are the two major dopaminergic areas in the brain. In view of this, and to focus insight into the neuronal functions caused by TGM2 mediated histone modifications at the Q residues, either serotonylation (for example, H3K4me3Q5 to H3K4me3Q5ser) in the context of cellular differentiation and signaling, or dopaminylation (for example, H3Q5 to H3Q5dop) in the dopaminergic VTA reward pathway and the precise role of cocaine withdrawal in this scenario are summarized and discussed in this contribution.

scholarly journals Repression of RNA message for F-box proteins in the tumors of patients with glioblastoma.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Brain Cancer ◽  
Gene Expression Analysis ◽  
Normal Brain ◽  
Significant Differential Expression ◽  
Differential Gene Expression Analysis ◽  
Genes Encoding ◽  
Differential Gene ◽  
The Brain ◽  
Median Survival Rate

Glioblastoma is the most common brain cancer in adults and has a 15 month median survival rate (1, 2). We performed differential gene expression analysis, comparing the glioblastoma transcriptome from 17 patients to the transcriptome of 8 non-affected, “normal” brain samples using a published dataset (3). Three separate genes encoding F-box proteins (4), including FBXW7, FBXO41, and FBXL16 were differentially expressed and at significantly lower levels in the tumors of patients with glioblastoma than in the brain. Significant differential expression of FBXW7, FBXO41 and FBXL16 was also observed in glioblastomas from the REMBRANDT study (5).

scholarly journals The Role of Phospholipase C in GABAergic Inhibition and Its Relevance to Epilepsy

2021 ◽  
Vol 22 (6) ◽  
pp. 3149
Author(s):  
Hye Yun Kim ◽  
Pann-Ghill Suh ◽  
Jae-Ick Kim
Keyword(s):  
Phospholipase C ◽  
Intracellular Signaling ◽  
Neuronal Development ◽  
Gabaergic Inhibition ◽  
Inhibitory Neurotransmitter ◽  
Intracellular Signaling Pathway ◽  
Key Enzyme ◽  
The Central Nervous System ◽  
Neuronal Functions ◽  
The Brain

Epilepsy is characterized by recurrent seizures due to abnormal hyperexcitation of neurons. Recent studies have suggested that the imbalance of excitation and inhibition (E/I) in the central nervous system is closely implicated in the etiology of epilepsy. In the brain, GABA is a major inhibitory neurotransmitter and plays a pivotal role in maintaining E/I balance. As such, altered GABAergic inhibition can lead to severe E/I imbalance, consequently resulting in excessive and hypersynchronous neuronal activity as in epilepsy. Phospholipase C (PLC) is a key enzyme in the intracellular signaling pathway and regulates various neuronal functions including neuronal development, synaptic transmission, and plasticity in the brain. Accumulating evidence suggests that neuronal PLC is critically involved in multiple aspects of GABAergic functions. Therefore, a better understanding of mechanisms by which neuronal PLC regulates GABAergic inhibition is necessary for revealing an unrecognized linkage between PLC and epilepsy and developing more effective treatments for epilepsy. Here we review the function of PLC in GABAergic inhibition in the brain and discuss a pathophysiological relationship between PLC and epilepsy.

scholarly journals Chemokines and chemokine receptors in the brain: implication in neuroendocrine regulation

2007 ◽  
Vol 38 (3) ◽  
pp. 355-363 ◽  
Author(s):  
Céline Callewaere ◽  
Ghazal Banisadr ◽  
William Rostène ◽  
Stéphane Mélik Parsadaniantz
Keyword(s):  
Chemokine Receptors ◽  
Cell Types ◽  
Normal Brain ◽  
Ability To Act ◽  
The Central Nervous System ◽  
Neuronal Functions ◽  
The Brain ◽  
Neuroendocrine Functions

Chemokines are small secreted proteins that chemoattract and activate immune and non-immune cells both in vivo and in vitro. In addition to their well-established role in the immune system, several recent reports have suggested that chemokines and their receptors may also play a role in the central nervous system (CNS). The best known central action is their ability to act as immunoinflammatory mediators. Indeed, these proteins regulate leukocyte infiltration in the brain during inflammatory and infectious diseases. However, we and others recently demonstrated that they are expressed not only in neuroinflammatory conditions, but also constitutively by different cell types including neurons in the normal brain, suggesting that they may act as modulators of neuronal functions. The goal of this review is to highlight the role of chemokines in the control of neuroendocrine functions. First, we will focus on the expression of chemokines and their receptors in the CNS, with the main spotlight on the neuronal expression in the hypothalamo–pituitary system. Secondly, we will discuss the role – we can now suspect – of chemokines and their receptors in the regulation of neuroendocrine functions. In conclusion, we propose that chemokines can be added to the well-described neuroendocrine regulatory mechanisms, providing an additional fine modulatory tuning system in physiological conditions.

scholarly journals Gene expression changes in the course of normal brain aging are sexually dimorphic

2008 ◽  
Vol 105 (40) ◽  
pp. 15605-15610 ◽  
Author(s):  
Nicole C. Berchtold ◽  
David H. Cribbs ◽  
Paul D. Coleman ◽  
Joseph Rogers ◽  
Elizabeth Head ◽  
...  
Keyword(s):  
Gene Expression ◽  
Entorhinal Cortex ◽  
Brain Aging ◽  
Expression Profiles ◽  
Later Life ◽  
Normal Brain ◽  
Sexually Dimorphic ◽  
Compensatory Mechanisms ◽  
Superior Frontal Gyrus ◽  
The Brain

Gene expression profiles were assessed in the hippocampus, entorhinal cortex, superior-frontal gyrus, and postcentral gyrus across the lifespan of 55 cognitively intact individuals aged 20–99 years. Perspectives on global gene changes that are associated with brain aging emerged, revealing two overarching concepts. First, different regions of the forebrain exhibited substantially different gene profile changes with age. For example, comparing equally powered groups, 5,029 probe sets were significantly altered with age in the superior-frontal gyrus, compared with 1,110 in the entorhinal cortex. Prominent change occurred in the sixth to seventh decades across cortical regions, suggesting that this period is a critical transition point in brain aging, particularly in males. Second, clear gender differences in brain aging were evident, suggesting that the brain undergoes sexually dimorphic changes in gene expression not only in development but also in later life. Globally across all brain regions, males showed more gene change than females. Further, Gene Ontology analysis revealed that different categories of genes were predominantly affected in males vs. females. Notably, the male brain was characterized by global decreased catabolic and anabolic capacity with aging, with down-regulated genes heavily enriched in energy production and protein synthesis/transport categories. Increased immune activation was a prominent feature of aging in both sexes, with proportionally greater activation in the female brain. These data open opportunities to explore age-dependent changes in gene expression that set the balance between neurodegeneration and compensatory mechanisms in the brain and suggest that this balance is set differently in males and females, an intriguing idea.

scholarly journals Probabilistic Critical Controllability Analysis of Protein Interaction Networks Integrating Normal Brain Ageing Gene Expression Profiles

2021 ◽  
Vol 22 (18) ◽  
pp. 9891
Author(s):  
Eimi Yamaguchi ◽  
Tatsuya Akutsu ◽  
Jose C. Nacher
Keyword(s):  
Gene Expression ◽  
Biological Networks ◽  
Expression Profiles ◽  
Dominating Set ◽  
Gene Expression Profiles ◽  
Brain Regions ◽  
Normal Brain ◽  
Age Related ◽  
Brain Ageing ◽  
The Brain

Recently, network controllability studies have proposed several frameworks for the control of large complex biological networks using a small number of life molecules. However, age-related changes in the brain have not been investigated from a controllability perspective. In this study, we compiled the gene expression profiles of four normal brain regions from individuals aged 20–99 years and generated dynamic probabilistic protein networks across their lifespan. We developed a new algorithm that efficiently identified critical proteins in probabilistic complex networks, in the context of a minimum dominating set controllability model. The results showed that the identified critical proteins were significantly enriched with well-known ageing genes collected from the GenAge database. In particular, the enrichment observed in replicative and premature senescence biological processes with critical proteins for male samples in the hippocampal region led to the identification of possible new ageing gene candidates.

scholarly journals SWI/SNF chromatin remodeler complex within the reward pathway is required for behavioral adaptations to stress

2021 ◽  
Author(s):  
Abdallah Zayed ◽  
Camille Baranowski ◽  
Anne Claire Compagnion ◽  
Cecile Vernochet ◽  
Samah Karaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Social Defeat ◽  
Global Scale ◽  
Chromatin Accessibility ◽  
Dopamine Neurons ◽  
Behavioral Adaptations ◽  
Atpase Subunits ◽  
Reward Pathway ◽  
Midbrain Dopamine ◽  
Preclinical And Clinical Studies

Stress exposure is a cardinal risk factor for most psychiatric diseases. Preclinical and clinical studies point to changes in gene expression involving epigenetic modifications within mesocorticolimbic brain circuits. Brahma (BRM) and Brahma-Related-Gene-1 (BRG1) are ATPase subunits of the SWI/SNF complexes involved in chromatin remodeling, a process essential to enduring plastic changes in gene expression. Here, we show that repeated social defeat induces changes in BRG1 nuclear distribution. The inactivation of the Brg1/Smarca4 gene within dopamine-innervated regions or the constitutive inactivation of the Brm/Smarca2 gene leads to resilience to repeated social defeat and decreases the behavioral responses to cocaine without impacting midbrain dopamine neurons activity. Within striatal medium spiny neurons Brg1 gene inactivation reduces the expression of stress- and cocaine-induced immediate early genes, increases levels of heterochromatin and at a global scale decreases chromatin accessibility. Altogether these data demonstrate the pivotal function of SWI/SNF complexes in behavioral and transcriptional adaptations to salient environmental challenges.

Fto-modulated lipid niche regulates adult neurogenesis through modulating adenosine metabolism

2020 ◽  
Vol 29 (16) ◽  
pp. 2775-2787
Author(s):  
Hui Gao ◽  
Xuejun Cheng ◽  
Junchen Chen ◽  
Chai Ji ◽  
Hongfeng Guo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adult Neurogenesis ◽  
Neuronal Development ◽  
Local Environment ◽  
Conditional Knockout ◽  
Neurogenic Niche ◽  
Altered Gene Expression ◽  
Altered Gene ◽  
Newborn Neurons ◽  
The Brain

Abstract Adult neurogenesis is regulated by diverse factors including the local environment, i.e. the neurogenic niche. However, whether the lipid in the brain regulates adult neurogenesis and related mechanisms remains largely unknown. In the present study, we found that lipid accumulates in the brain during postnatal neuronal development. Conditional knockout of Fto (cKO) in lipid not only reduced the level of lipid in the brain but also impaired the learning and memory of mice. In addition, Fto deficiency in lipid did not affect the proliferation of adult neural stem cells (aNSCs), but it did inhibit adult neurogenesis by inducing cell apoptosis. Mechanistically, specific deleting Fto in lipid altered gene expression and increased adenosine secretion of adipocytes. The treatment of adenosine promoted the apoptosis of newborn neurons. As a whole, these results reveal the important function of the lipid niche and its associated mechanism in regulating adult neurogenesis.

Neonatal Ogg1/Mutyh knockout mice have altered inflammatory gene response compared to wildtype mice in the brain and lung after hypoxia-reoxygenation

2018 ◽  
Vol 47 (1) ◽  
pp. 114-124 ◽  
Author(s):  
Anne Gro W. Rognlien ◽  
Embjørg J. Wollen ◽  
Monica Atneosen-Åsegg ◽  
Rajikala Suganthan ◽  
Magnar Bjørås ◽  
...  
Keyword(s):  
Gene Expression ◽  
Knockout Mice ◽  
A Priori ◽  
Gene Activation ◽  
Dna Glycosylase ◽  
Double Knockout ◽  
Inflammatory Gene ◽  
Gene Response ◽  
The Brain ◽  
Hypoxia Reoxygenation

Abstract Background 8-Oxoguanine DNA-glycosylase 1 (OGG1) and mutY DNA glycosylase (MUTYH) are crucial in the repair of the oxidative DNA lesion 7,8-dihydro-8-oxoguanine caused by hypoxia-reoxygenation injury. Our objective was to compare the gene expression changes after hypoxia-reoxygenation in neonatal Ogg1-Mutyh double knockout mice (OM) and wildtype mice (WT), and study the gene response in OM after hyperoxic reoxygenation compared to normoxic. Methods Postnatal day 7 mice were subjected to 2 h of hypoxia (8% O2) followed by reoxygenation in either 60% O2 or air, and sacrificed right after completed reoxygenation (T0h) or after 72 h (T72h). The gene expression of 44 a priori selected genes was examined in the hippocampus/striatum and lung. Results We found that OM had an altered gene response compared to WT in 21 genes in the brain and 24 genes in the lung. OM had a lower expression than WT of inflammatory genes in the brain at T0h, and higher expression at T72h in both the brain and lung. In the lung of OM, five genes were differentially expressed after hyperoxic reoxygenation compared to normoxic. Conclusion For the first time, we report that Ogg1 and Mutyh in combination protect against late inflammatory gene activation in the hippocampus/striatum and lung after neonatal hypoxia-reoxygenation.

scholarly journals Neural Functions of Matrix Metalloproteinases: Plasticity, Neurogenesis, and Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Hiromi Fujioka ◽  
Yusuke Dairyo ◽  
Kei-ichiro Yasunaga ◽  
Kazuo Emoto
Keyword(s):  
Extracellular Matrix ◽  
Nervous System ◽  
Matrix Metalloproteinases ◽  
Neuronal Development ◽  
Neuronal Circuits ◽  
Intrinsic Factors ◽  
Neuronal Disease ◽  
Brain Changes ◽  
Neuronal Functions ◽  
The Brain

The brain changes in response to experience and altered environment. To do that, the nervous system often remodels the structures of neuronal circuits. This structural plasticity of the neuronal circuits appears to be controlled not only by intrinsic factors, but also by extrinsic mechanisms including modification of the extracellular matrix. Recent studies employing a range of animal models implicate that matrix metalloproteinases regulate multiple aspects of the neuronal development and remodeling in the brain. This paper aims to summarize recent advances of our knowledge on the neuronal functions of matrix metalloproteinases and discuss how they might relate in neuronal disease.

Back to the basics? Transcriptomics offers integrative insights into the role of space, time and the environment for gene expression and behaviour

2021 ◽  
Vol 17 (9) ◽  
pp. 20210293
Author(s):  
Eva K. Fischer ◽  
Mark E. Hauber ◽  
Alison M. Bell
Keyword(s):  
Gene Expression ◽  
Rna Sequencing ◽  
Molecular Basis ◽  
Gene Activation ◽  
Rna Expression ◽  
Brain Gene Expression ◽  
Explicit Consideration ◽  
The Brain ◽  
Genomic Revolution

Fuelled by the ongoing genomic revolution, broadscale RNA expression surveys are fast replacing studies targeting one or a few genes to understand the molecular basis of behaviour. Yet, the timescale of RNA-sequencing experiments and the dynamics of neural gene activation are insufficient to drive real-time switches between behavioural states. Moreover, the spatial, functional and transcriptional complexity of the brain (the most commonly targeted tissue in studies of behaviour) further complicates inference. We argue that a Central Dogma-like ‘back-to-basics’ assumption that gene expression changes cause behaviour leaves some of the most important aspects of gene–behaviour relationships unexplored, including the roles of environmental influences, timing and feedback from behaviour—and the environmental shifts it causes—to neural gene expression. No perfect experimental solutions exist but we advocate that explicit consideration, exploration and discussion of these factors will pave the way toward a richer understanding of the complicated relationships between genes, environments, brain gene expression and behaviour over developmental and evolutionary timescales.

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