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Journal ArticleDOI: 10.1080/10253890.2020.1759548

Social defeat stress affects resident's clock gene and bdnf expression in the brain.

04 Mar 2021-Stress (Stress)-Vol. 24, Iss: 2, pp 206-212
Abstract: Social defeat stress affects behavior and changes the expression of the genes underlying neuronal plasticity in the brain. The circadian clock regulates most neuronal processes in the brain, which results in daily variations of complex behavior, and any disturbance in circadian clock oscillations increases the risk of mood and cognitive disbalance. In this study, we assessed the effect of acute and repeated social defeat stress on Per2 and Nr1d1 expression in prefrontal cortexes, hippocampi, pineal glands, olfactory bulbs, cerebella, and pituitary glands. We also evaluated the effect of our experimental setting on levels of Bdnf and plasma corticosterone, two markers widely used to asses the impact of stress on mammalian physiology. Our data show that single and repeated social defeat stress upregulates the expression of both clock genes and Bdnf in all brain structures, and corticosterone in the blood. While the general pattern of Bdnf upregulation suggests higher sensitivity in the intruder group, the clock genes are induced more significantly in residents, especially by repeated stress sessions. Our work thus suggests that the model of stress-induced anxiety and depression should consider a group of residents because, for some parameters, they may respond more distinctively than intruders.LAY SUMMARYThe resident/intruder experimental paradigm affects the expression of clock genes Per2, Nr1d1and Bdnf in the brain structures and plasma corticosterone level. The induction of clock genes is evident in both experimental groups; however, it is more marked in residents. Together with the significant increase in Bdnf levels in the majority of brain structures and plasma corticosterone in residents, our data suggest that in the model of social defeat stress, the utility of an experimental group of residents could be contributive.

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Topics: Social defeat (59%), CLOCK (53%), Brain-derived neurotrophic factor (53%) ... show more
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6 results found


Open accessJournal ArticleDOI: 10.3389/FNINS.2021.646678
Barbara Gisabella1, Jobin Babu1, Jake Valeri1, Lindsay Rexrode1  +1 moreInstitutions (1)
Abstract: Sleep disturbances and memory dysfunction are key characteristics across psychiatric disorders. Recent advances have revealed insight into the role of sleep in memory consolidation, pointing to key overlap between memory consolidation processes and structural and molecular abnormalities in psychiatric disorders. Ongoing research regarding the molecular mechanisms involved in memory consolidation has the potential to identify therapeutic targets for memory dysfunction in psychiatric disorders and aging. Recent evidence from our group and others points to extracellular matrix molecules, including chondroitin sulfate proteoglycans and their endogenous proteases, as molecules that may underlie synaptic dysfunction in psychiatric disorders and memory consolidation during sleep. These molecules may provide a therapeutic targets for decreasing strength of reward memories in addiction and traumatic memories in PTSD, as well as restoring deficits in memory consolidation in schizophrenia and aging. We review the evidence for sleep and memory consolidation dysfunction in psychiatric disorders and aging in the context of current evidence pointing to the involvement of extracellular matrix molecules in these processes.

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1 Citations


Open accessJournal ArticleDOI: 10.3389/FGENE.2021.754198
Usui Noriyoshi1, Yuta Ono1, Ryoko Aramaki1, Stefano Berto2  +3 moreInstitutions (4)
Abstract: Early life stress (ELS), such as abuse, neglect, and maltreatment, exhibits a strong impact on the brain and mental development of children. However, it is not fully understood how ELS affects social behaviors and social-associated behaviors as well as developing prefrontal cortex (PFC). In this study, we performed social isolation on weaned pre-adolescent mice until adolescence and investigated these behaviors and PFC characteristics in adolescent mice. We found the ELS induced social impairments in social novelty, social interaction, and social preference in adolescent mice. We also observed increases of anxiety-like behaviors in ELS mice. In histological analysis, we found a reduced number of neurons and an increased number of microglia in the PFC of ELS mice. To identify the gene associated with behavioral and histological features, we analyzed transcriptome in the PFC of ELS mice and identified 15 differentially expressed genes involved in transcriptional regulation, stress, and synaptic signaling. Our study demonstrates that ELS influences social behaviors, anxiety-like behaviors through cytoarchitectural and transcriptomic alterations in the PFC of adolescent mice.

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Topics: Social behavior (53%), Prefrontal cortex (52%), Synaptic signaling (52%) ... show more

Open accessJournal ArticleDOI: 10.1038/S41386-021-01219-8
Abstract: The multifactorial etiology of stress-related disorders necessitates a constant interrogation of the molecular convergences in preclinical models of stress that use disparate paradigms as stressors spanning from environmental challenges to genetic predisposition to hormonal signaling. Using RNA-sequencing, we investigated the genomic signatures in the ventral hippocampus common to mouse models of stress. Chronic oral corticosterone (CORT) induced increased anxiety- and depression-like behavior in wild-type male mice and male mice heterozygous for the gene coding for brain-derived neurotrophic factor Val66Met, a variant associated with genetic susceptibility to stress. In a separate set of male mice, chronic social defeat stress (CSDS) led to a susceptible or a resilient population, whose proportion was dependent on housing conditions, namely standard housing or enriched environment. Rank-rank-hypergeometric overlap (RRHO), a threshold-free approach that ranks genes by their p value and effect size direction, was used to identify genes from a continuous gradient of significancy that were concordant across groups. In mice treated with CORT and in standard-housed susceptible mice, differentially expressed genes (DEGs) were concordant for gene networks involved in neurotransmission, cytoskeleton function, and vascularization. Weighted gene co-expression analysis generated 54 gene hub modules and revealed two modules in which both CORT and CSDS-induced enrichment in DEGs, whose function was concordant with the RRHO predictions, and correlated with behavioral resilience or susceptibility. These data showed transcriptional concordance across models in which the stress coping depends upon hormonal, environmental, or genetic factors revealing common genomic drivers that embody the multifaceted nature of stress-related disorders.

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Topics: Genetic predisposition (51%), Population (51%)

Open accessJournal ArticleDOI: 10.1016/J.YNSTR.2021.100328
Abstract: Social rank functions to facilitate coping responses to socially stressful situations and conditions. The evolution of social status appears to be inseparably connected to the evolution of stress. Stress, aggression, reward, and decision-making neurocircuitries overlap and interact to produce status-linked relationships, which are common among both male and female populations. Behavioral consequences stemming from social status and rank relationships are molded by aggressive interactions, which are inherently stressful. It seems likely that the balance of regulatory elements in pro- and anti-stress neurocircuitries results in rapid but brief stress responses that are advantageous to social dominance. These systems further produce, in coordination with reward and aggression circuitries, rapid adaptive responding during opportunities that arise to acquire food, mates, perch sites, territorial space, shelter and other resources. Rapid acquisition of resources and aggressive postures produces dominant individuals, who temporarily have distinct fitness advantages. For these reasons also, change in social status can occur rapidly. Social subordination results in slower and more chronic neural and endocrine reactions, a suite of unique defensive behaviors, and an increased propensity for anxious and depressive behavior and affect. These two behavioral phenotypes are but distinct ends of a spectrum, however, they may give us insights into the troubling mechanisms underlying the myriad of stress-related disorders to which they appear to be evolutionarily linked.

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Topics: Aggression (55%), Dominance (ethology) (53%)

Open accessJournal ArticleDOI: 10.17179/EXCLI2021-3764
04 Jun 2021-Excli Journal
Abstract: In this review article, we aimed to discuss the role of sleep deprivation (SD) in learning and memory processing in basic and clinical studies. There are numerous studies investigating the effect of SD on memory, while most of these studies have shown the impairment effect of SD. However, some of these studies have reported conflicting results, indicating that SD does not impair memory performance or even improves it. So far, no study has discussed or compared the conflicting results of SD on learning and memory. Thus, this important issue in the neuroscience of sleep remains unknown. The main goal of this review article is to compare the similar mechanisms between the impairment and the improvement effects of SD on learning and memory, probably leading to a scientific solution that justifies these conflicting results. We focused on the inconsistent effects of SD on some mechanisms involved in learning and memory, and tried to discuss the inconsistent effects of SD on learning and memory.

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References
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53 results found


Journal ArticleDOI: 10.1126/SCIENCE.1120972
10 Feb 2006-Science
Abstract: Mice experiencing repeated aggression develop a long-lasting aversion to social contact, which can be normalized by chronic, but not acute, administration of antidepressant. Using viral-mediated, mesolimbic dopamine pathway-specific knockdown of brain-derived neurotrophic factor (BDNF), we showed that BDNF is required for the development of this experience-dependent social aversion. Gene profiling in the nucleus accumbens indicates that local knockdown of BDNF obliterates most of the effects of repeated aggression on gene expression within this circuit, with similar effects being produced by chronic treatment with antidepressant. These results establish an essential role for BDNF in mediating long-term neural and behavioral plasticity in response to aversive social experiences.

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Topics: Mesolimbic pathway (59%), Social defeat (57%), Brain-derived neurotrophic factor (56%) ... show more

1,709 Citations


Open accessJournal ArticleDOI: 10.1073/PNAS.0609625104
Kole T. Roybal1, David Theobold1, Ami Graham1, Jennifer A. DiNieri2  +12 moreInstitutions (4)
Abstract: Circadian rhythms and the genes that make up the molecular clock have long been implicated in bipolar disorder. Genetic evidence in bipolar patients suggests that the central transcriptional activator of molecular rhythms, CLOCK, may be particularly important. However, the exact role of this gene in the development of this disorder remains unclear. Here we show that mice carrying a mutation in the Clock gene display an overall behavioral profile that is strikingly similar to human mania, including hyperactivity, decreased sleep, lowered depression-like behavior, lower anxiety, and an increase in the reward value for cocaine, sucrose, and medial forebrain bundle stimulation. Chronic administration of the mood stabilizer lithium returns many of these behavioral responses to wild-type levels. In addition, the Clock mutant mice have an increase in dopaminergic activity in the ventral tegmental area, and their behavioral abnormalities are rescued by expressing a functional CLOCK protein via viral-mediated gene transfer specifically in the ventral tegmental area. These findings establish the Clock mutant mice as a previously unrecognized model of human mania and reveal an important role for CLOCK in the dopaminergic system in regulating behavior and mood.

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Topics: CLOCK (65%), CLOCK Proteins (59%), Ventral tegmental area (55%) ... show more

695 Citations


Open accessJournal ArticleDOI: 10.1016/J.NEURON.2012.04.006
Urs Albrecht1Institutions (1)
26 Apr 2012-Neuron
Abstract: The mammalian circadian system, which is comprised of multiple cellular clocks located in the organs and tissues, orchestrates their regulation in a hierarchical manner throughout the 24 hr of the day. At the top of the hierarchy are the suprachiasmatic nuclei, which synchronize subordinate organ and tissue clocks using electrical, endocrine, and metabolic signaling pathways that impact the molecular mechanisms of cellular clocks. The interplay between the central neural and peripheral tissue clocks is not fully understood and remains a major challenge in determining how neurological and metabolic homeostasis is achieved across the sleep-wake cycle. Disturbances in the communication between the plethora of body clocks can desynchronize the circadian system, which is believed to contribute to the development of diseases such as obesity and neuropsychiatric disorders. This review will highlight the relationship between clocks and metabolism, and describe how cues such as light, food, and reward mediate entrainment of the circadian system.

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Topics: Circadian clock (58%)

591 Citations


Open accessJournal ArticleDOI: 10.1016/J.BRAINRES.2013.09.033
Gaurav Patki1, Naimesh Solanki1, Fatin Atrooz1, Farida Allam1  +1 moreInstitutions (1)
20 Nov 2013-Brain Research
Abstract: In the present study, we have examined the behavioral and biochemical effect of induction of psychological stress using a modified version of the resident-intruder model for social stress (social defeat). At the end of the social defeat protocol, body weights, food and water intake were recorded, depression and anxiety-like behaviors as well as memory function was examined. Biochemical analysis including oxidative stress measurement, inflammatory markers and other molecular parameters, critical to behavioral effects were examined. We observed a significant decrease in the body weight in the socially defeated rats as compared to the controls. Furthermore, social defeat increased anxiety-like behavior and caused memory impairment in rats (P<0.05). Socially defeated rats made significantly more errors in long term memory tests (P<0.05) as compared to control rats. Furthermore, brain extracellular signal-regulated kinase-1/2 (ERK1/2), and an inflammatory marker, interleukin (IL)-6 were activated (P<0.05), while the protein levels of glyoxalase (GLO)-1, glutathione reductase (GSR)-1, calcium/calmodulin-dependent protein kinase type (CAMK)-IV, cAMP-response-element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) were significantly less (P<0.05) in the hippocampus, but not in the prefrontal cortex and amygdala of socially defeated rats, when compared to control rats. We suggest that social defeat stress alters ERK1/2, IL-6, GLO1, GSR1, CAMKIV, CREB, and BDNF levels in specific brain areas, leading to oxidative stress-induced anxiety-depression-like behaviors and as well as memory impairment in rats.

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Topics: Social defeat (59%), Social stress (57%), Brain-derived neurotrophic factor (54%) ... show more

255 Citations


Open accessJournal ArticleDOI: 10.1093/NAR/GKS1161
Abstract: CircaDB (http://circadb.org) is a new database of circadian transcriptional profiles from time course expression experiments from mice and humans. Each transcript’s expression was evaluated by three separate algorithms, JTK_Cycle, Lomb Scargle and DeLichtenberg. Users can query the gene annotations using simple and powerful full text search terms, restrict results to specific data sets and provide probability thresholds for each algorithm. Visualizations of the data are intuitive charts that convey profile information more effectively than a table of probabilities. The CircaDB web application is open source and available at http:// github.com/itmat/circadb.

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233 Citations