Circadian disruption in mice through chronic jetlag-like conditions modulates molecular profiles of cancer in nucleus accumbens and prefrontal cortex

2021 ◽  
Author(s):  
Suliman Khan ◽  
V Wee Yong ◽  
Mengzhou Xue
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Pet Imaging ◽  
Biological Rhythms ◽  
Brain Regions ◽  
Molecular Signature ◽  
Environmental Light ◽  
Positron Emission ◽  
The Individual ◽  
Risk Of Cancer

Abstract Biological rhythms regulate physiological activities. Shiftwork disrupts normal circadian rhythms and may increase the risk of cancer through unknown mechanisms. To mimic environmental light/dark changes encountered by shift workers, a protocol called “chronic jet lag (CJL)” induced by repeatedly shifting light-dark cycles has been used. Here, we subjected mice to CJL by advancing light–dark cycle by 6 hours every 2 days, and conducted RNA sequencing to analyze the expression profile and molecular signature in the brain areas of prefrontal cortex and nucleus accumbens. We also performed positron emission tomography (PET) imaging to monitor changes related to glucose metabolism in brain. Our results reveal systematic reprogramming of gene expression associated with cancer related pathways and metabolic pathways in prefrontal cortex and nucleus accumbens. PET imaging indicates that glucose uptake level was significantly reduced in whole brain as well as the individual brain regions. Moreover, qPCR analysis describes that the expression levels of cancer related genes were altered in prefrontal cortex and nucleus accumbens. Overall, these results suggest a molecular and metabolic link with CJL mediated cancer risk, and generate hypotheses on how CJL increases the susceptibility to cancer.

scholarly journals Clozapine impact on FosB/ΔFosB expression in stress preconditioned rats: response to a novel stressor

2019 ◽  
Vol 53 (2) ◽  
pp. 83-92
Author(s):  
Jana Osacka ◽  
Lubica Horvathova ◽  
Alena Cernackova ◽  
Alexander Kiss
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Medial Prefrontal Cortex ◽  
Acute Stress ◽  
Chronic Mild Stress ◽  
Brain Regions ◽  
Prolonged Treatment ◽  
Mild Stress ◽  
Nucleus Accumbens Shell ◽  
The Individual

AbstractObjective. Prolonged treatment with neuroleptics has been shown to induce FosB/ΔFosB expression in several brain regions including the medial prefrontal cortex, dorsomedial and dorsolateral striatum, ventrolateral and dorsolateral septum, nucleus accumbens shell and core, and the hypothalamic paraventricular nucleus (PVN). Some of these regions are known to be also stress responsive. This study was designed to determine whether repeated clozapine (CLZ) administration for 7 consecutive days to Wistar rats may modify FosB/ΔFosB expression in the above-mentioned brain areas induced by acute stress or novel stressor that followed 13-day chronic mild stress preconditioning.Methods. Following experimental groups were used: unstressed animals treated with vehicle/ CLZ for 7 days; 7-day vehicle/CLZ-treated animals on the last day exposed to acute stress – forced swimming (FSW); and animals preconditioned with stress for 13 days treated from the 8th day with vehicle/CLZ and on the 14th day exposed to novel stress – FSW.Results. In the unstressed animals CLZ markedly increased FosB/ΔFosB immunoreactivity in the ventrolateral septum and PVN. FSW elevated FosB/ΔFosB expression in the medial prefrontal cortex, striatum, and septum. CLZ markedly potentiated the effect of the FSW on FosB/ΔFosB expression in the PVN, but suppressed it in the dorsomedial striatum. Novel stress with stress preconditioning increased FosB/ΔFosB immunoreactivity in the prefrontal cortex, striatum, ventrolateral septum, and the PVN. In the nucleus accumbens the effect of the novel stressor was potentiated by CLZ.Conclusion. Our data indicate that CLZ may modulate the acute as well as novel stress effects on FosB/ΔFosB expression but its effect differs within the individual brain regions.

scholarly journals Expression of Dopamine-Related Genes in Four Human Brain Regions

2020 ◽  
Vol 10 (8) ◽  
pp. 567
Author(s):  
Ansley Grimes Stanfill ◽  
Xueyuan Cao
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Substantia Nigra ◽  
Human Brain ◽  
Demographic Characteristic ◽  
Treatment Options ◽  
Tissue Expression ◽  
Brain Regions ◽  
Future Treatment ◽  
Psychiatric Conditions

A better understanding of dopaminergic gene expression will inform future treatment options for many different neurologic and psychiatric conditions. Here, we utilized the National Institutes of Health’s Genotype-Tissue Expression project (GTEx) dataset to investigate genotype by expression associations in seven dopamine pathway genes (ANKK1, DBH, DRD1, DRD2, DRD3, DRD5, and SLC6A3) in and across four human brain tissues (prefrontal cortex, nucleus accumbens, substantia nigra, and hippocampus). We found that age alters expression of DRD1 in the nucleus accumbens and prefrontal cortex, DRD3 in the nucleus accumbens, and DRD5 in the hippocampus and prefrontal cortex. Sex was associated with expression of DRD5 in substantia nigra and hippocampus, and SLC6A3 in substantia nigra. We found that three linkage disequilibrium blocks of SNPs, all located in DRD2, were associated with alterations in expression across all four tissues. These demographic characteristic associations and these variants should be further investigated for use in screening, diagnosis, and future treatment of neurological and psychiatric conditions.

2Hz-Electroacupuncture Attenuates Conditioned Cue-Evoked Heroin-Seeking Behavior and Increase CB2-Rs Expression in Relapse-Relevant Brain Regions in Heroin-Addicted Rats

2014 ◽  
Vol 998-999 ◽  
pp. 164-168 ◽  
Author(s):  
Lin Chen ◽  
Bao Miao Ma ◽  
Kai Yue ◽  
Qin Ru ◽  
Xiang Tian ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Rat Model ◽  
Fixed Ratio ◽  
Brain Regions ◽  
Inhibitory Effect ◽  
Control Group ◽  
Self Administration ◽  
Seeking Behavior

In order to investigate the influence of electroacupuncture on heroin seeking behavior and the expression of CB2-Rs in the relapse-relevant brain regions, heroin self-administration rat model which represents the heroin relapse behaviors was developed with progressive fixed ratio program. The model rats were randomly divided into 3 groups: control group, heroin-addicted group and 2Hz electroacupuncture group (stimulating on acupoints zusanli and sanyinjiao). The expression of CB2-Rs in the relapse-relevant brain regions were assessed with immunohistochemistry technologies. The reinstatement of heroin seeking behavior induced by conditioned cue priming showed that compared with the heroin-addicted group, active pokes in the 2Hz electroacupuncture group decreased significantly (p<0.05). Compared with the control group, the expression of CB2-Rs in prefrontal cortex (PFC) and nucleus accumbens (NAc) was significantly decreased (p<0.05) in heroin-addicted group and increaseed significantly recover (p<0.05) in the 2Hz electroacupuncture group. Our present results showed that 2Hz-electroacupuncture could attenuate the conditioned cue-evoked heroin-seeking behavior and the inhibitory effect was mediated partially by the increase CB2-Rs expression in relapse-relevant brain regions in heroin-addicted rats.

scholarly journals 2Hz-Electroacupuncture Attenuates Heroin-Seeking Behaviors via Adjusts CB1-Rs and CB2-Rs Expression in Relapse-Relevant Brain Regions of Heroin Self-Administration Rats

2019 ◽  
pp. 835-844
Author(s):  
L. CHEN ◽  
X.-K. GONG ◽  
C.-L. LENG ◽  
B.-M. MA ◽  
Q. RU ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Ventral Tegmental Area ◽  
Brain Regions ◽  
High Rate ◽  
Opiate Addiction ◽  
Control Group ◽  
Self Administration ◽  
Ventral Tegmental

Opiate addiction has a high rate of relapse. The accumulating evidence shows that electroacupuncture (EA) may be effective for the treatment of opiate relapse. However, the change of expression of CB1-Rs and CB2-Rs involve in 2Hz EA anti-relapse pathway is still unclear. To explore the changes of expression of CB1-Rs and CB2-Rs, heroin self-administration (SA) model rats were adopted and treated using 2Hz EA. The expressions of CB1-Rs and CB2-Rs were observed using immunohistochemistry method. The results showed that, compared with the control group, active pokes in the heroin-addicted group increased, while the active pokes decreased significantly in 2Hz EA group compared with heroin-addicted group. Correspondingly, the expression of CB1-Rs in prefrontal cortex (PFC), hippocampus (Hip), nucleus accumbens (NAc) and ventral tegmental area (VTA) all increased significantly while the expression of CB2-Rs in those relapse-relevant brain regions decreased obviously in heroin-addicted group when compared with the control group. In addition, the expression of CB1-Rs obviously decreased in the 2Hz EA group while the expression of CB2-Rs in those relapse-relevant brain regions increased significantly when compared with the heroin-addicted group. It indicated that 2Hz EA could attenuate the heroin-evoked seeking behaviors effectively. The anti-relapse effects of 2Hz EA might be related to the decrease of CB1-Rs and increase of CB2-Rs expression in relapse-relevant brain regions of heroin SA rats.

scholarly journals Luxotonic signals in human prefrontal cortex: A possible substrate for effects of light on mood and cognition

2020 ◽  
Author(s):  
Shai Sabbah ◽  
Michael S. Worden ◽  
Daniel Laniado ◽  
Rebeca Waugh ◽  
David M. Berson ◽  
...  
Keyword(s):  
Motor Control ◽  
Prefrontal Cortex ◽  
Visual Processing ◽  
Bright Light ◽  
Luminance Level ◽  
Brain Regions ◽  
Reward Processing ◽  
Subcortical Structures ◽  
Environmental Light ◽  
Mood And Cognition

AbstractLight impacts mood and cognition of humans and other animals in ways we are only beginning to recognize. These effects are thought to depend upon a specialized retinal output signal arising from intrinsically photosensitive retinal ganglion cells (ipRGCs) that is being dedicated to a stable representation of the intensity of environmental light. Insights from animal studies now implicate a previously unknown pathway in the effects of environmental light on mood. A subset of ipRGCs transmits light-intensity information to the dorsothalamic perihabenular nucleus, which in turn, innervates the medial prefrontal cortex that plays a key role in mood regulation. While the prefrontal cortex has been implicated in depression and other mood disorders, its ability to encode the level of environmental light (luminance) has never been reported. Here, as a first step to probing for a similar retino-thalamo-frontocortical circuit in humans, we used functional magnetic resonance imaging (fMRI) to identify brain regions in which activity depended on luminance level where activity was modulated either transiently or persistently by light. Twelve brain regions altered their steady-state activity according to luminance level. Most were in the prefrontal cortex or in the classic thalamocortical visual pathway; others were found in the cerebellum, caudate, and pineal. Prefrontal cortex and pineal exhibited reduced BOLD signal in bright light, while the other centers exhibited increased BOLD signals. The light-evoked prefrontal response was affected by light history and closely resembled those of ipRGCs. Although we did not find clear correspondence between the luxotonic regions in humans and those in mice, the persistence and luxotonic nature of light-evoked responses in the human prefrontal cortex may suggest that it receives input from ipRGCs, just like in the mouse. We also found seventeen regions in which activity varied only transiently with luminance level. These regions, which are involved in visual processing, motor control, and cognition, were in the cerebral cortex, diverse subcortical structures, and cerebellum. Therefore, our results demonstrate the effects of light on diverse brain centers that contribute to motor control, cognition, emotion, and reward processing.

scholarly journals Integrative Analysis of Global Gene Expression Identifies Opposite Patterns of Reactive Astrogliosis in Aged Human Prefrontal Cortex

2018 ◽  
Author(s):  
César Payán-Gómez ◽  
Diego Rodríguez ◽  
Diana Amador-Munoz ◽  
Sandra Ramirez
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Brain Aging ◽  
Global Gene Expression ◽  
Brain Regions ◽  
Molecular Signature ◽  
Analytic Approximation ◽  
Shh Pathway ◽  
Transcriptomic Signature ◽  
First Time

Prefrontal cortex (PFC) is one of the brain regions with more prominent changes in human aging. The molecular processes related to the aging cognitive decline and mood changes are not completely understood. In order to improve our knowledge, we integrated transcriptomic data of four studies of human PFC from old people -58-80 years old- compared with young people -20-40 years old- using a meta-analytic approximation combined with molecular signature analysis. We identified 1816 differentially expressed genes -561 up-regulated and 1256 down-regulated. Pathway analysis revealed down-regulation of synaptic genes with conservation of gene expression of other neuronal regions. Additionally, we identified up-regulation of markers of astrogliosis with transcriptomic signature compatible with A1 neurotoxic astrocytes and A2 neuroprotective astrocytes. Response to interferon is related to A1 astrocytes and the A2 phenotype is mediated in aging by activation of SHH pathway and up-regulation of metallothioneins I and genes of the family EZR -ezrin, radixin, and moesin-. The main conclusions of our study are the confirmation that in aged PFC there is a global dysfunction of the synapses and we reported for the first time opposite phenotypes of astrogliosis because of brain aging.

scholarly journals [18F]-T807 tauopathy PET imaging in chronic traumatic encephalopathy

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 229 ◽  
Author(s):  
Sam Gandy ◽  
Steven T. DeKosky
Keyword(s):  
Pet Imaging ◽  
Brain Injuries ◽  
Chronic Traumatic Encephalopathy ◽  
Neurofibrillary Tangle ◽  
Brain Regions ◽  
Tracer Uptake ◽  
Positron Emission ◽  
Molecular Ligand ◽  
Mesial Temporal Lobe ◽  
Recent Case Report

A new molecular ligand for positron emission tomography (PET) of the human brain, [18F]-T807, is under investigation for the antemortem detection of pathological neurofibrillary aggregates, which are evidence of neurofibrillary tangle (NFT) diseases, also known as tauopathies. Repetitive mild traumatic brain injuries in athletes and battlefield veterans are associated with one such tauopathy, known as chronic traumatic encephalopathy (CTE). In a recent case report, a former NFL player with clinically probable CTE and a concurrent Progressive Supranuclear Palsy (PSP) –like syndrome was studied using [18F]-T807. The interpretation of this player’s [18F]-T807 PET imaging was complicated by the overlap of tracer uptake in brain regions involved in CTE and PSP with regions associated with either nonspecific [18F]-T807 ligand binding or “aging-associated” binding of [18F]-T807 to authentic tauopathy known to be associated with aging and disease severity (i.e., NFT in the mesial temporal lobe). The implications of these data for the utility of [18F]-T807 in the pre-mortem detection of CTE are summarized.

scholarly journals Brain Regional Gene Expression Network Analysis Identifies Unique Interactions Between Chronic Ethanol Exposure and Consumption

2019 ◽  
Author(s):  
M.L. Smith ◽  
M.F. Lopez ◽  
A.R. Wolen ◽  
H.C. Becker ◽  
M.F. Miles
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Network Analysis ◽  
Drinking Behavior ◽  
Ethanol Consumption ◽  
Brain Regions ◽  
Ethanol Exposure ◽  
Functional Enrichment ◽  
Regional Gene

AbstractProgressive increases in ethanol consumption is a hallmark of alcohol use disorder (AUD). Persistent changes in brain gene expression are hypothesized to underlie the altered neural signaling producing abusive consumption in AUD. To identify brain regional gene expression networks contributing to progressive ethanol consumption, we performed microarray and scale-free network analysis of expression responses in a C57BL/6J mouse model utilizing chronic intermittent ethanol by vapor chamber (CIE) in combination with limited access oral ethanol consumption. This model has previously been shown to produce long-lasting increased ethanol consumption, particularly when combining oral ethanol access with repeated cycles of intermittent vapor exposure. The interaction of CIE and oral consumption was studied by expression profiling and network analysis in medial prefrontal cortex, nucleus accumbens, hippocampus, bed nucleus of the stria terminalis, and central nucleus of the amygdala. Brain region expression networks were analyzed for ethanol-responsive gene expression, correlation with ethanol consumption and functional content using extensive bioinformatics studies. In all brain-regions studied the largest number of changes in gene expression were seen when comparing ethanol naïve mice to those exposed to CIE and drinking. In the prefrontal cortex, however, unique patterns of gene expression were seen compared to other brain-regions. Network analysis identified modules of co-expressed genes in all brain regions. The prefrontal cortex and nucleus accumbens showed the greatest number of modules with significant correlation to drinking behavior. Across brain-regions, however, many modules with strong correlations to drinking, both baseline intake and amount consumed after CIE, showed functional enrichment for synaptic transmission and synaptic plasticity.

Relationship of monoamine oxidase A binding to adaptive and maladaptive personality traits

2010 ◽  
Vol 41 (5) ◽  
pp. 1051-1060 ◽  
Author(s):  
A. Soliman ◽  
R. M. Bagby ◽  
A. A. Wilson ◽  
L. Miler ◽  
M. Clark ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Monoamine Oxidase ◽  
Personality Traits ◽  
Brain Regions ◽  
Monoamine Oxidase A ◽  
Neo Personality Inventory ◽  
Positron Emission ◽  
Neo Personality Inventory Revised ◽  
Factor Regression ◽  
Depressive Episodes

BackgroundMonoamine oxidase A (MAOA) is an important enzyme that metabolizes monoamines such as serotonin, norepinephrine and dopamine in the brain. In prefrontal cortex, low MAOA binding is associated with aggression and high binding is associated with major depressive disorder (MDD) and also risk for recurrence of depressive episodes. In rodent models, low MAOA levels are associated with increased aggression and fear conditioning, and decreased social and exploratory investigative behaviors. Our objective was to measure MAOA binding in prefrontal cortex and concurrently evaluate a broad range of validated personality traits. We hypothesized that prefrontal MAOA binding would correlate negatively with angry-hostility, a trait related to aggression/anger, and positively with traits intuitively related to adaptive investigative behavior.MethodParticipants were aged 19–49 years, healthy and non-smoking. MAOA binding was measured with [11C]harmine positron emission tomography (PET) in prefrontal brain regions and personality traits were measured with the NEO Personality Inventory Revised (NEO PI-R).ResultsPrefrontal MAOA binding correlated negatively with angry-hostility (r=−0.515, p=0.001) and positively with deliberation (r=0.514, p=0.001). In a two-factor regression model, these facets explained 38% of variance in prefrontal MAOA binding. A similar relationship was found in prefrontal cortex subregions.ConclusionsWe propose a new continuum describing the relationship between personality and MAOA: deliberate/thoughtful contrasting aggressive/impulsive. Additionally, the association between high MAOA binding and greater deliberation may explain why some people have moderately high levels of MAOA, although very high levels occur during MDD. In health, higher MAOA binding is associated with an adaptive personality facet.

scholarly journals Vulnerability to psychotogenic effects of ketamine is associated with elevated D2/3-receptor availability

2013 ◽  
Vol 16 (4) ◽  
pp. 745-754 ◽  
Author(s):  
Ingo Vernaleken ◽  
Majken Klomp ◽  
Olaf Moeller ◽  
Mardjan Raptis ◽  
Arne Nagels ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Young Male ◽  
Brain Regions ◽  
Psychotic Symptoms ◽  
Placebo Condition ◽  
Affinity Ligand ◽  
Positron Emission ◽  
Syndrome Scale ◽  
The Face ◽  
The Individual

Abstract Previous positron emission tomography (PET) studies employing competition paradigms have shown either no change or substantial declines in striatal [11C]-raclopride binding after challenge with psychotogenic doses of the N-methyl-d-aspartate antagonist ketamine. We sought to probe the relationship between the severity of ketamine-induced psychotic symptoms and altered dopamine D2/3 receptor availability throughout brain using the high affinity ligand [18F]-fallypride (FP). PET recordings were obtained in a group of 10 healthy, young male volunteers, in a placebo condition, and in the course of an infusion with ketamine at a psychotomimetic dose. Administration of the Positive and Negative Syndrome Scale and the Thought and Language Index in both conditions revealed a substantial emergence of mainly negative symptoms of schizophrenia, persisting until the end of the 3 h PET recordings. The baseline FP binding in cortex, caudate nucleus and other brain regions was highly predictive of the individual severity of psychotic symptoms in the ketamine condition. However, there was no evidence of ketamine-evoked reductions in FP binding. In the context of earlier findings, we speculate that high baseline D2/3-receptor availability may impart benefits with regard to cognitive flexibility, but increases the risk of maladaptive information processing in the face of environmental stresses and challenges.

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