Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA148495 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:MAP kinase signaling has been implicated in brain development, long-term memory, and the response to antidepressants. Inducible Braf knockout mice enabled us to unravel a new role of neuronal MAPK signaling for emotional behavior. Braf mice that were induced during adulthood showed normal anxiety but increased depression-like behavior, in accordance with pharmacological findings. In contrast, the inactivation of Braf in the juvenile brain leads to normal depression-like behavior but decreased anxiety in adults. In these mutants we found no alteration of GABAergic neurotransmission but reduced neuronal arborization in the dentate gyrus. Analysis of gene expression in the hippocampus revealed nine downregulated MAPK target genes that represent candidates to cause the mutant phenotype. Our results reveal the differential function of MAPK signaling in juvenile and adult life phases and emphasize the early postnatal period as critical for the determination of anxiety in adults. Moreover, these results validate inducible gene inactivation as new valuable approach, allowing to discriminate between gene function in the adult and the developing postnatal brain.
2012-04-19 | GSE33618 | GEO
Project description:MAP kinase signaling has been implicated in brain development, long-term memory, and the response to antidepressants. Inducible Braf knockout mice enabled us to unravel a new role of neuronal MAPK signaling for emotional behavior. Braf mice that were induced during adulthood showed normal anxiety but increased depression-like behavior, in accordance with pharmacological findings. In contrast, the inactivation of Braf in the juvenile brain leads to normal depression-like behavior but decreased anxiety in adults. In these mutants we found no alteration of GABAergic neurotransmission but reduced neuronal arborization in the dentate gyrus. Analysis of gene expression in the hippocampus revealed nine downregulated MAPK target genes that represent candidates to cause the mutant phenotype. Our results reveal the differential function of MAPK signaling in juvenile and adult life phases and emphasize the early postnatal period as critical for the determination of anxiety in adults. Moreover, these results validate inducible gene inactivation as new valuable approach, allowing to discriminate between gene function in the adult and the developing postnatal brain. Five male Braf-cko, six male homozygous Braf-flox littermates, six male heterozygous CamkII-Cre, and six male wildtype littermates were killed with CO2, the complete hippocampal tissue was prepared, and total RNA was extracted with the Trizol protocol. The integrity and quality of the RNA samples were analyzed with an RNA electrophoresis chip (RNA 6000 Nano Kit, Agilent, Boeblingen, Germany). RNA samples of high integrity and quality (RIN ≥ 7.5) were further processed with the TotalPrep RNA Amplification Kit (Ambion, Austin, TX, USA) and hybridized onto MouseWG-6 v1.1 Expression Bead-Chips (Illumina, San Diego, CA, USA) following manufacturer’s instructions. Data were analyzed using the software R (used packages: beadarray, limma, and vsn).
2012-04-18 | E-GEOD-33618 | biostudies-arrayexpress
Project description:Investigating the molecular basis and correlates of anxiety-related and depression-like behaviors, we generated a mouse model consisting of high (HAB), normal (NAB) and low (LAB) anxiety-related behavior mice. We utilized the elevated plus-maze for testing the genetic predisposition to anxiety-related behavior and, consequently, used this as selection criterion for the inbreeding of our animals. In depression-related tests, HAB mice display a more passive, depression-like coping strategy than LAB mice, resembling clinical comorbidity of anxiety and depression as observed in psychiatric patients. Using a microarray approach, the hypothalamic paraventricular nucleus (PVN), the basolateral (BLA) and central amygdala (CeA), the cingulate cortex (Cg) and the dentate gyrus (DG) – centers of the central nervous anxiety and fear circuitries – were investigated and screened for differences between HAB, NAB and LAB mice. Analysis was performed from four to six animals per line (HAB, NAB and LAB from generation 25, respectively) per brain region, giving a total of 78 individual arrays analyzed. The LAB mouse line is referred to as reference.
2011-05-04 | E-GEOD-29014 | biostudies-arrayexpress
Project description:Investigating the molecular basis and correlates of anxiety-related and depression-like behaviors, we generated a mouse model consisting of high (HAB) and low (LAB) anxiety-related behavior mice. We utilized the elevated plus-maze for testing the genetic predisposition to anxiety-related behavior and, consequently, used this as selection criterion for the inbreeding of our animals. In depression-related tests, HAB mice display a more passive, depression-like coping strategy than LAB mice, resembling clinical comorbidity of anxiety and depression as observed in psychiatric patients. Using a microarray approach, the hypothalamic paraventricular nucleus (PVN), the basolateral/lateral (BLA), the medial (MeA) and central amygdala (CeA), the nucleus accumbens (NAc), the cingulate cortex (Cg) and the supraoptic nucleus (SON) – centers of the central nervous anxiety and fear circuitries – were investigated and screened for differences between HAB and LAB mice. Analysis was performed from six animals per line (HAB and LAB, respectively) pooled per brain region in ten technical replicates, thereof five with a dye-swapped design giving a total of 70 array slides analyzed. The LAB mouse line is referred to as reference.
2011-08-29 | E-GEOD-28999 | biostudies-arrayexpress
Project description:Individual differences in human temperament can increase the risk of psychiatric disorders like depression and anxiety. Our laboratory utilized a rat model of temperamental differences to assess neurodevelopmental factors underlying emotional behavior differences. Rats selectively bred for low novelty exploration (Low Responders, LR) display high levels of anxiety- and depression-like behavior compared to High Novelty Responder (HR) rats. Using transcriptome profiling, the present study uncovered vast gene expression differences in the early postnatal HR versus LR limbic brain, including changes in genes involved in cellular metabolism. These data led us to hypothesize that rats prone to high (versus low) anxiety/depression-like behavior exhibit distinct patterns of brain metabolism during the first weeks of life, which may reflect disparate patterns of synaptogenesis and brain circuit development. All samples were generated from Sprague-Dawley male rats selectively bred for high novelty response (HRs) or low novelty response (LRs).
2016-09-20 | GSE87082 | GEO
Project description:Investigating the molecular basis and correlates of anxiety-related and depression-like behaviors, we generated a mouse model consisting of high (HAB), normal (NAB) and low (LAB) anxiety-related behavior mice. We utilized the elevated plus-maze for testing the genetic predisposition to anxiety-related behavior and, consequently, used this as selection criterion for the inbreeding of our animals. In depression-related tests, HAB mice display a more passive, depression-like coping strategy than LAB mice, resembling clinical comorbidity of anxiety and depression as observed in psychiatric patients. Using a microarray approach, the hypothalamic paraventricular nucleus (PVN), the basolateral (BLA) and central amygdala (CeA), the cingulate cortex (Cg) and the dentate gyrus (DG) – centers of the central nervous anxiety and fear circuitries – were investigated and screened for differences between HAB, NAB and LAB mice.
2011-05-04 | GSE29014 | GEO
Project description:Investigating the molecular basis and correlates of anxiety-related and depression-like behaviors, we generated a mouse model consisting of high (HAB) and low (LAB) anxiety-related behavior mice. We utilized the elevated plus-maze for testing the genetic predisposition to anxiety-related behavior and, consequently, used this as selection criterion for the inbreeding of our animals. In depression-related tests, HAB mice display a more passive, depression-like coping strategy than LAB mice, resembling clinical comorbidity of anxiety and depression as observed in psychiatric patients. Using a microarray approach, the hypothalamic paraventricular nucleus (PVN), the basolateral/lateral (BLA), the medial (MeA) and central amygdala (CeA), the nucleus accumbens (NAc), the cingulate cortex (Cg) and the supraoptic nucleus (SON) – centers of the central nervous anxiety and fear circuitries – were investigated and screened for differences between HAB and LAB mice.
2011-08-30 | GSE28999 | GEO
Project description:Brain structure and function are sexually dimorphic. As neuroscience research has largely focused on the male brain and behavior, the female brain and, in particular, its inherent dynamics have been left underexplored. During the mammalian reproductive period, the female brain is exposed to fluctuating hormone levels over the cycles known as menstrual (in humans) or estrous (in rodents). Variation in estradiol levels has been shown to affect synaptic plasticity in the female brain, including changes in dendritic spine density systematically across the estrous cycle. Female emotionality and cognitive function vary with physiologically fluctuating sex hormone levels. However, the molecular mechanisms underlying the dynamic nature of the female brain structure and function are currently unknown. Here we show that neuronal chromatin organization in the female ventral hippocampus of mouse is dynamic and fluctuates across the estrous cycle. We find changes in chromatin organization associated with the transcriptional activity of nearby genes important for neuronal function, neurotransmission, synapse formation, and behavior. We also link these chromatin dynamics to variation in anxiety-like behavior and to fluctuations in dendritic spine and synaptic density in the ventral hippocampus. In terms of chromatin structure, within-female and between-sex variation are of similar magnitudes, emphasizing the importance of accounting for fluctuating sex-hormone levels in females in the studies of the brain epigenome and behavior. These results provide critical insights into the mechanisms underlying sex-hormone and sex-dependent variation in adult brain structure and function. The study also has implications for better understanding of sex-biased disorders such as depression and anxiety which are strongly associated with sex-hormone status in females and are twice as prevalent in women than in men. This study establishes a foundation for the development of sex-specific approaches to treat sex-biased neuropsychiatric disorders including depression and anxiety disorders.
2019-05-03 | GSE114036 | GEO
Project description:Complex mixtures of persistent organic pollutants (POPs) are regularly detected in the environment and animal tissues. Often these chemicals are associated with latent effects following early-life exposures, following the developmental origin of health and disease paradigm. We investigated the long-term effects of a human relevant mixture of 29 POPs on adult zebrafish following a developmental exposure, in addition to a single PFOS exposure for comparison, as it was the compound with the highest concentration within the mixture. Zebrafish embryos were exposed from 6 to 96 hours post fertilization to x10 and x70 the level of POP mixture or PFOS found in human blood before being transferred to clean water. We measured growth, swimming performance, and reproductive output at different life stages. In addition, we assessed anxiety behavior of the adults and their offspring, as well as performing a transcriptomic analysis on the adult zebrafish brain, as the POP mixture and PFOS concentrations used are known to affect larval behavior. Exposure to POP mixture and PFOS reduced swimming performance and increased length and weight, compared to controls. No effect of developmental exposure was observed on reproductive output or anxiety behavior. Additionally, RNA-seq did not reveal pathways related to anxiety although pathways related to synapse biology were affected at the x10 PFOS level. Furthermore, pathway analysis of the brain transcriptome of adults exposed as larvae to the low concentration of PFOS revealed enrichment in pathways such as calcium, MAPK, and GABA signaling, all of which are important for learning and memory. Based on our results we can conclude that some effects on the endpoints measured were apparent, but if these effects lead to adversities at population levels remains elusive.
2020-12-03 | GSE162503 | GEO
Project description:Depression is one of the most common neuropsychiatric disorders. Although the pathogenesis of depression is still unknown, environmental risk factors and genetics are implicated. Copper (Cu), a cofactor of multiple enzymes, is involved in regulating depression-related processes. Depressed patients carrying the apolipoprotein ε4 allele display more severe depressive symptoms, indicating that ApoE4 is closely associated with an increased risk of depression. The study explored the effect of low-dose Cu (0.13 ppm) exposure and ApoE4 on depression-like behavior of mice and further investigate the possible mechanisms. The 4-month-old ApoE4 mice and wild-type (WT) mice were treated with 0.13 ppm CuCl2 for 4 months. After the treatment, ApoE4 mice displayed obvious depression-like behavior compared with the WT mice, and Cu exposure further exacerbated the depression-like behavior of ApoE4 mice. There was no significant difference in anxiety behavior (Open field test) and memory behavior (Morris water maze). Proteomic analysis revealed that the differentially expressed proteins between Cu-exposed and non-exposed ApoE4 mice were mainly involved in Ras signaling pathway, protein export, axon guidance, serotonergic synapse, GABAergic synapse, dopaminergic synapse. Among these differentially expressed proteins, immune response and synaptic function are highly correlated. Representative protein expression changes are quantified by Western blot, showing consistent results as determined by proteomic analysis. Hippocampal astrocytes and microglia were increased in Cu-exposed ApoE4 mice, suggesting that neuroglial cells played an important role in the pathogenesis of depression. Taken together, our study demonstrated that Cu exposure exacerbates depression-like behavior of ApoE4 mice and the mechanisms may involve the dysregulation of synaptic function and immune response, and overactivation of neuroinflammation.
2021-09-09 | PXD022422 | Pride