Project description:We carried out untargeted metabolomics of the prefrontal cortex of rats exposed to chronic social isolation (CSIS), a rat model of depression, and/or fluoxetine treatment using liquid chromatography-high resolution mass spectrometry.
Project description:The depressive-like behavior in animals is usually assessed by standardized behavioral tests such as the forced swimming test. However, the findings of these tests may be affected by individual variability among animals, which may hinder the discovery of genes responsible for depression. Few reports have showed the influence of individual variability in identifying the genes associated with depressive-like behavior. In this study, we measured the immobility ratio (% immobility in 5 min) in the forced swimming test in 106 male Wistar rats. According to the distribution of individual immobility ratio, the rats were divided into three groups: the control group with immobility ratio -1 to +1 standard deviation (SD) from the mean, the depressive group with immobility ratio +1 to +2 SD above the mean, and the anti-depressive group with immobility ratio -1 to -2 SD below the mean. Microarray analysis was used to identify the genes differentially expressed by depressive group rats in the prefrontal cortex and cerebellum. The differentially expressed genes in both brain regions of the depressive group were Alas2, Gh1, Hba-a2, Hbb, Hbb-b1, Hbe2, LOC689064, Mrps10, Mybpc, Olf6415, and Pfkb1. Ingenuity pathway analysis identified Gh1 as a hub gene in the networks of the differentially expressed genes in both brain regions. This study indicates that inherent differences in depressive-like behavior may be related to the Gh1 expression in the cerebellum and prefrontal cortex. We measured the immobility ratio of 106 normal rats using the forced swimming test and statistically analysis. We selected the rats exhibitting depressive-like behavior or average in the 106 rats. Total RNA was prepareted from the cerebellum and prefrontal cortex. An equal amount of RNA from 4 rats in each group was pooled and used for microarray analysis.
Project description:The early-life environment critically influences neurodevelopment and later psychological health. To elucidate neural and environmental elements that shape emotional behavior, we developed a rat model of individual differences in temperament and environmental reactivity. We selectively bred rats for high versus low behavioral response to novelty and found that high-reactive (bred high-responder, bHR) rats displayed greater risk-taking, impulsivity and aggression relative to low-reactive (bred low-responder, bLR) rats, which showed high levels of anxiety/depression-like behavior and certain stress vulnerability. The bHR/bLR traits are heritable, but prior work revealed bHR/bLR maternal style differences, with bLR dams showing more maternal attention than bHRs. The present study implemented a cross-fostering paradigm to examine the contribution of maternal behavior to the brain development and emotional behavior of bLR offspring. bLR offspring were reared by biological bLR mothers or fostered to a bLR or bHR mother and then evaluated to determine the effects on the developmental gene expression in the hippocampus and amygdala. Genome-wide expression profiling showed that cross-fostering bLR rats to bHR mothers shifted developmental gene expression in the amygdala (but not hippocampus). All samples were generated from Sprague-Dawley male rats selectively bred for high novelty response (HRs), low novelty response (LRs) or LRs that were crossfostered to either a LR dame or HR dame.
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.
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.
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.
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.
Project description:The bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) is often detected in blood of patient’s presenting at emergency rooms with a psychosis-like syndrome involving agitation, panic, confusion/cognitive impairment, violent behavior, depression, and other adverse behavioral symptoms. The mechanisms underlying MDPV’s behavioral disturbances and its effect on brain gene expression patterns, particularly effects of chronic use on genetic changes in striatum and cortex are unknown. Such changes in gene expression are expected to reflect altered changes in brain function and structure as a consequence of MDPV abuse. A major objective of these experiments is to determine the relationship between repeated MDPV exposure and genes encoding dopaminergic, vascular, central inflammatory markers (e.g., IL6, IL10, IL1β, IFNγ, TNFα), particularly in prefrontal cortex, striatum, hypothalamus, and amygdala.
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).