scholarly journals Epigenetic Regulatory Dynamics in Models of Methamphetamine-Use Disorder

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1614
Author(s):  
Subramaniam Jayanthi ◽  
Michael T. McCoy ◽  
Jean Lud Cadet
Keyword(s):  
Gene Expression ◽  
Brain Regions ◽  
Reward Processing ◽  
Post Translational Modifications ◽  
Methamphetamine Use ◽  
Underlying Mechanisms ◽  
Induced Changes ◽  
Methamphetamine Use Disorder ◽  
Disease Exposure

Methamphetamine (METH)-use disorder (MUD) is a very serious, potentially lethal, biopsychosocial disease. Exposure to METH causes long-term changes to brain regions involved in reward processing and motivation, leading vulnerable individuals to engage in pathological drug-seeking and drug-taking behavior that can remain a lifelong struggle. It is crucial to elucidate underlying mechanisms by which exposure to METH leads to molecular neuroadaptive changes at transcriptional and translational levels. Changes in gene expression are controlled by post-translational modifications via chromatin remodeling. This review article focuses on the brain-region specific combinatorial or distinct epigenetic modifications that lead to METH-induced changes in gene expression.

scholarly journals Methamphetamine-induced changes in myocardial gene transcription are sex-dependent

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hasitha Chavva ◽  
Daniel A. Brazeau ◽  
James Denvir ◽  
Donald A. Primerano ◽  
Jun Fan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ischemic Injury ◽  
Female Rats ◽  
Dependent Effect ◽  
Methamphetamine Use ◽  
Number Of Genes ◽  
Myocardial Ischemic Injury ◽  
Induced Changes ◽  
Myocardial Gene Expression

Abstract Background Prior work demonstrated that female rats (but not their male littermates) exposed to methamphetamine become hypersensitive to myocardial ischemic injury. Importantly, this sex-dependent effect persists following 30 days of subsequent abstinence from the drug, suggesting that it may be mediated by long term changes in gene expression that are not rapidly reversed following discontinuation of methamphetamine use. The goal of the present study was to determine whether methamphetamine induces sex-dependent changes in myocardial gene expression and whether these changes persist following subsequent abstinence from methamphetamine. Results Methamphetamine induced changes in the myocardial transcriptome were significantly greater in female hearts than male hearts both in terms of the number of genes affected and the magnitude of the changes. The largest changes in female hearts involved genes that regulate the circadian clock (Dbp, Per3, Per2, BMal1, and Npas2) which are known to impact myocardial ischemic injury. These genes were unaffected by methamphetamine in male hearts. All changes in gene expression identified at day 11 returned to baseline by day 30. Conclusions These data demonstrate that female rats are more sensitive than males to methamphetamine-induced changes in the myocardial transcriptome and that methamphetamine does not induce changes in myocardial transcription that persist long term after exposure to the drug has been discontinued.

scholarly journals Three Years Follow-Up Study Showed Prenatal Methamphetamine Exposure May Cause Chronic Abnormalities In Transcriptomic Pattern

2021 ◽  
Author(s):  
Arvin Haghighatfard ◽  
Soha Seifollahi ◽  
Pegah Rajabi ◽  
Niloofar Rahmani ◽  
Rojin Ghannadzadeh
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Rna Extraction ◽  
Childbearing Age ◽  
Methamphetamine Use ◽  
Methamphetamine Use Disorder

Abstract Background: The high rate of methamphetamine use disorder among young adults and women of childbearing age makes it imperative to clarify the long-term effects of Methamphetamine exposure on the offspring. Behavioral and cognitive problems had been reported in children with parental Methamphetamine exposure (PME). The present study aimed to assess the acute and chronic effects of PME in molecular regulations and gene expression profiles of children during their first years of life.Methods: All subjects were recruited before birth, and sampling was conducted from the first ten days of birth, twelve months, twenty months, and thirty-six months of age. Finally, 2658 children with PME and 3573 normal children had been finished the follow-up. RNA extraction was operated from blood samples and gene expression profiling was conducted by using the Affymetrix GeneChip Human Genome U133 plus 2.0 Array Platform. Gene expression data were confirmed by Real-time PCR. Results: Gene expression profiling during thirty-six months showed several constant mRNA level alterations in children with PME compared with normal. These genes are involved in several gene ontologies and pathways involved with the immune system, neuronal functions, and bioenergetic metabolism. It seems that Methamphetamine use disorder before and during the pregnancy period may affect the expression profile of children, and these changes could remain years after birth. Affected genes have some similarities with the gene expression patterns of addiction, psychiatric disorders, neurodevelopmental disabilities, and immune deficiencies. Conclusion: Findings may shed light on the molecular effects of prenatal methamphetamine exposure and may lead to new psychological and somatic caring protocols for these children based on their potential abnormalities.

scholarly journals Mechanisms Underlying Motivational Dysfunction in Schizophrenia

2021 ◽  
Vol 15 ◽  
Author(s):  
Youssuf Saleh ◽  
Isaac Jarratt-Barnham ◽  
Emilio Fernandez-Egea ◽  
Masud Husain
Keyword(s):  
Negative Symptoms ◽  
Brain Regions ◽  
Reward Processing ◽  
Diagnostic Methods ◽  
Pharmacological Intervention ◽  
Brain Disorders ◽  
Treatment Development ◽  
Frontal Brain ◽  
Behavioural Insights ◽  
Underlying Mechanisms

Negative symptoms are a debilitating feature of schizophrenia which are often resistant to pharmacological intervention. The mechanisms underlying them remain poorly understood, and diagnostic methods rely on phenotyping through validated questionnaires. Deeper endo-phenotyping is likely to be necessary in order to improve current understanding. In the last decade, valuable behavioural insights have been gained through the use of effort-based decision making (EBDM) tasks. These have highlighted impairments in reward-related processing in schizophrenia, particularly associated with negative symptom severity. Neuroimaging investigations have related these changes to dysfunction within specific brain networks including the ventral striatum (VS) and frontal brain regions. Here, we review the behavioural and neural evidence associated with negative symptoms, shedding light on potential underlying mechanisms and future therapeutic possibilities. Findings in the literature suggest that schizophrenia is characterised by impaired reward based learning and action selection, despite preserved hedonic responses. Associations between amotivation and reward-processing deficits have not always been clear, and may be mediated by factors including cognitive dysfunction or dysfunctional or self-defeatist beliefs. Successful endo-phenotyping of negative symptoms as a function of objective behavioural and neural measurements is crucial in advancing our understanding of this complex syndrome. Additionally, transdiagnostic research–leveraging findings from other brain disorders, including neurological ones–can shed valuable light on the possible common origins of motivation disorders across diseases and has important implications for future treatment development.

Cardiovascular Effects of Particulate Air Pollution

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Aruni Bhatnagar
Keyword(s):  
Fossil Fuels ◽  
Fine Particulate Matter ◽  
Cardiovascular Effects ◽  
Premature Mortality ◽  
Annual Review ◽  
Publication Date ◽  
Particulate Air Pollution ◽  
Underlying Mechanisms ◽  
Disease Exposure

Inhalation of fine particulate matter (PM2.5), produced by the combustion of fossil fuels, is an important risk factor for cardiovascular disease. Exposure to PM2.5 has been linked to increases in blood pressure, thrombosis, and insulin resistance. It also induces vascular injury and accelerates atherogenesis. Results from animal models corroborate epidemiological evidence and suggest that the cardiovascular effects of PM2.5 may be attributable, in part, to oxidative stress, inflammation, and the activation of the autonomic nervous system. Although the underlying mechanisms remain unclear, there is robust evidence that long-term exposure to PM2.5 is associated with premature mortality due to heart failure, stoke, and ischemic heart disease. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Adaptive and multifunctional hydrogel hybrid probes for long-term sensing and modulation of neural activity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Seongjun Park ◽  
Hyunwoo Yuk ◽  
Ruike Zhao ◽  
Yeong Shin Yim ◽  
Eyob W. Woldeghebriel ◽  
...  
Keyword(s):  
Foreign Body ◽  
Brain Regions ◽  
Foreign Body Response ◽  
Behavioral Studies ◽  
Hydrogel Matrix ◽  
Underlying Mechanisms ◽  
Hybrid Devices ◽  
The Brain ◽  
Body Response

AbstractTo understand the underlying mechanisms of progressive neurophysiological phenomena, neural interfaces should interact bi-directionally with brain circuits over extended periods of time. However, such interfaces remain limited by the foreign body response that stems from the chemo-mechanical mismatch between the probes and the neural tissues. To address this challenge, we developed a multifunctional sensing and actuation platform consisting of multimaterial fibers intimately integrated within a soft hydrogel matrix mimicking the brain tissue. These hybrid devices possess adaptive bending stiffness determined by the hydration states of the hydrogel matrix. This enables their direct insertion into the deep brain regions, while minimizing tissue damage associated with the brain micromotion after implantation. The hydrogel hybrid devices permit electrophysiological, optogenetic, and behavioral studies of neural circuits with minimal foreign body responses and tracking of stable isolated single neuron potentials in freely moving mice over 6 months following implantation.

scholarly journals The Impact of Sports-Related Concussions on the Language System

2018 ◽  
Vol 1 (1) ◽  
pp. 36-46
Author(s):  
Patrick S Ledwidge
Keyword(s):  
Brain Activity ◽  
Brain Regions ◽  
Functional Brain Imaging ◽  
Long Term Effects ◽  
Brain Potentials ◽  
Language System ◽  
Induced Changes ◽  
The Impact ◽  
Language Network

Sports-related Concussions (SRC) and their potential long-term effects are a growing concern among athletes and their families. Research utilizing functional brain imaging/recording techniques (e.g., fMRI, ERP) seeks to explain how neurocognitive brain activity changes in the days and years following SRC. Although language deficits are documented following non-sports related concussion there remains a striking lack of research on how SRCs may influence the language system and their supporting neural mechanisms. Neuroimaging findings, however, demonstrate that SRCs alter structural and functional pathways within the frontotemporal language network. Brain regions included in this network generate language-related event-related brain potentials (ERPs), including the N400 and P600. ERPs have been used to demonstrate long-term neurocognitive alterations associated with concussion and may also provide objective and robust markers of SRC-induced changes to the language system.

scholarly journals Epigenetics of Hepatic Insulin Resistance

2021 ◽  
Vol 12 ◽  
Author(s):  
Hannah Maude ◽  
Claudia Sanchez-Cabanillas ◽  
Inês Cebola
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Prolonged Exposure ◽  
Current Knowledge ◽  
Hepatic Insulin Resistance ◽  
Metabolic Dysfunction ◽  
Post Translational Modifications ◽  
Targeted Interventions ◽  
Insulin Resistant

Insulin resistance (IR) is largely recognized as a unifying feature that underlies metabolic dysfunction. Both lifestyle and genetic factors contribute to IR. Work from recent years has demonstrated that the epigenome may constitute an interface where different signals may converge to promote IR gene expression programs. Here, we review the current knowledge of the role of epigenetics in hepatic IR, focusing on the roles of DNA methylation and histone post-translational modifications. We discuss the broad epigenetic changes observed in the insulin resistant liver and its associated pathophysiological states and leverage on the wealth of ‘omics’ studies performed to discuss efforts in pinpointing specific loci that are disrupted by these changes. We envision that future studies, with increased genomic resolution and larger cohorts, will further the identification of biomarkers of early onset hepatic IR and assist the development of targeted interventions. Furthermore, there is growing evidence to suggest that persistent epigenetic marks may be acquired over prolonged exposure to disease or deleterious exposures, highlighting the need for preventative medicine and long-term lifestyle adjustments to avoid irreversible or long-term alterations in gene expression.

scholarly journals Wiskott-Aldrich syndrome protein is an effector of Kit signaling

Blood ◽  
2009 ◽  
Vol 114 (14) ◽  
pp. 2900-2908 ◽  
Author(s):  
Maheswaran Mani ◽  
Shivkumar Venkatasubrahmanyam ◽  
Mrinmoy Sanyal ◽  
Shoshana Levy ◽  
Atul Butte ◽  
...  
Keyword(s):  
Gene Expression ◽  
Positive Culture ◽  
Selective Advantage ◽  
Heterozygous Female ◽  
Interacting Protein ◽  
Wiskott Aldrich Syndrome ◽  
Underlying Mechanisms ◽  
And Migration ◽  
Induced Changes ◽  
Syndrome Protein

The pleiotropic receptor tyrosine kinase Kit can provide cytoskeletal signals that define cell shape, positioning, and migration, but the underlying mechanisms are less well understood. In this study, we provide evidence that Kit signals through Wiskott-Aldrich syndrome protein (WASP), the central hematopoietic actin nucleation-promoting factor and regulator of the cytoskeleton. Kit ligand (KL) stimulation resulted in transient tyrosine phosphorylation of WASP, as well as interacting proteins WASP-interacting protein and Arp2/3. KL-induced filopodia in bone marrow–derived mast cells (BMMCs) were significantly decreased in number and size in the absence of WASP. KL-dependent regulation of intracellular Ca2+ levels was aberrant in WASP-deficient BMMCs. When BMMCs were derived from WASP-heterozygous female mice using KL as a growth factor, the cultures eventually developed from a mixture of WASP-positive and -negative populations into a homogenous WASP-positive culture derived from the WASP-positive progenitors. Thus, WASP expression conferred a selective advantage to the development of Kit-dependent hematopoiesis consistent with the selective advantage of WASP-positive hematopoietic cells observed in WAS-heterozygous female humans. Finally, KL-mediated gene expression in wild-type and WASP-deficient BMMCs was compared and revealed that approximately 30% of all Kit-induced changes were WASP dependent. The results indicate that Kit signaling through WASP is necessary for normal Kit-mediated filopodia formation, cell survival, and gene expression, and provide new insight into the mechanism in which WASP exerts a strong selective pressure in hematopoiesis.

Roles of CREB Signaling Pathway in Regulation of Fear Memory

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
S. Kida
Keyword(s):  
Gene Expression ◽  
Gene Expression Regulation ◽  
Fear Memory ◽  
Brain Regions ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
New Gene ◽  
Activity Dependent

Activity-dependent gene expression through activation of Ca2+-CREB signal transduction pathways has been thought to play a central role in fear memory formation. On the other hand, retrieval of fear memory triggers two time-dependent phases of reactivated memory; reconsolidation and extinction. To understand the mechanisms for determining the fate of the reactivated fear memory, we investigated roles of CREB in reconsolidation and extinction of contextual fear memory and then analyzed the brain-regions regulating reconsolidation and extinction by identifying regions where CREB-mediated gene expression is activated and then examining the role of protein synthesis in those regions on reconsolidation and extinction. We first showed that activation of CREB-mediated transcription is required for reconsolidation and long-term extinction of contextual fear memory. Using immunocytochemical analyses, we demonstrated that CREB is activated in the hippocampus/amygdala and amygdala/medial prefrontal cortex (mPFC) in the reconsolidation and extinction phases, respectively. Similar results were observed by analyzing the expression of a CREB-dependent gene, Arc. We finally showed that reconsolidation and long-term extinction of the contextual fear memory depended on new gene expression in the hippocampus/amygdala and amygdala/mPFC, respectively. Thus reactivated contextual fear memory is reconsolidated or extinguished through distinct CREB-mediated gene expression regulation in the hippocampus, amygdala and mPFC.

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