Differential expression of Dusp1 and immediate early response genes in hippocampus of rats, subjected to forced swimming test
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE162524 | GEO | 2023/02/27
REPOSITORIES: GEO
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Project description:The forced swim test (FST) is widely used to screen for potential antidepressant drugs and treatments. Despite this, the nature of stillness during FST and whether it resembles "depressive-like behavior" are widely debated issues. Furthermore, despite being widely used as a behavioral assay, the effects of the FST on the brain transcriptome are rarely investigated. Therefore, in this study we have investigated changes in the transcriptome of the rat hippocampus 20 min and 24 h after FST exposure. RNA-Seq is performed on the hippocampus tissues of rats 20 min and 24 h after an FST. Differentially expressed genes (DEGs) were identified using limma and used to construct gene interaction networks. Fourteen differentially expressed genes (DEGs) were identified only in the 20-m group. No DEGs were identified 24 h after the FST. These genes were used for Gene Ontology term enrichment and gene-network construction. Based on the constructed gene-interaction networks, we identified a group of DEGs (Dusp1, Fos, Klf2, Ccn1, and Zfp36) that appeared significant based on multiple methods of downstream analysis. Dusp1 appears especially important, as its role in the pathogenesis of depression has been demonstrated both in various animal models of depression and in patients with depressive disorders.
| S-EPMC10281975 | biostudies-literature
Project description:Differential expression of Dusp1 and immediate early response genes in hippocampus of rats, subjected to forced swimming test
| PRJNA682164 | ENA
Project description:The circadian clock system is associated with feeding and mood. Patients with night eating syndrome (NES) delay their eating rhythm and their mood declines during the evening and night, manifesting as time-specific depression. Therefore, we hypothesized that the NES feeding pattern might cause time-specific depression. We established new NES model by restricted feeding with high-fat diet during the inactive period under normal-fat diet ad libitum. The FST (forced swimming test) immobility time in the NES model group was prolonged only after lights-on, corresponding to evening and early night for humans. We examined the effect of the NES feeding pattern on peripheral clocks using PER2::LUCIFERASE knock-in mice and an in vivo monitoring system. Caloric intake during the inactive period would shift the peripheral clock, and might be an important factor in causing the time-specific depression-like behavior. In the NES model group, synthesis of serotonin and norepinephrine were increased, but utilization and metabolism of these monoamines were decreased under stress. Desipramine shortened some mice's FST immobility time in the NES model group. The present study suggests that the NES feeding pattern causes phase shift of peripheral clocks and malfunction of the monoamine system, which may contribute to the development of time-specific depression.
| S-EPMC5773531 | biostudies-other
Project description:AimSelective serotonin reuptake inhibitors (SSRIs) are used to treat major depressive disorder (MDD) and other psychiatric disorders (e.g., obsessive compulsive disorder, social anxiety disorder, and panic disorder). In MDD treatment, SSRIs do not show remission in approximately 30% of patients, indicating a need for a better treatment option. Forced swimming test (FST) is a behavioral assay to evaluate depression-like behavior and antidepressant efficacy in rodents. In the present study, we evaluated the combination effect of brexpiprazole with SSRIs on FST in mice, in order to investigate their synergistic effect.MethodsBrexpiprazole (0.003 mg/kg) was intraperitoneally injected to mice 15 min before testing. Escitalopram (10 mg/kg), fluoxetine (75 mg/kg), paroxetine (10 mg/kg), or sertraline (15 mg/kg) were orally administered to mice 60 min before testing. Then, the mice were placed in water and immobility time was measured. Data from animals treated with escitalopram, fluoxetine, paroxetine, and sertraline were pooled as SSRI-treated group data.ResultsCombination treatment of brexpiprazole with SSRIs reduced immobility time in FST more than vehicle or each single treatment. A significant interaction effect was confirmed in the combination of brexpiprazole and SSRIs (p = 0.0411).ConclusionEfficacy of adjunctive brexpiprazole has already been demonstrated in clinical trials in MDD patients not adequately responding to antidepressants including escitalopram, fluoxetine, paroxetine, and sertraline. The synergistic antidepressant-like effect of brexpiprazole with SSRIs found in this study supports the already known clinical findings.
| S-EPMC10009414 | biostudies-literature
Project description:BackgroundMany neuropsychiatric disorders, including stress-related mood disorders, are complex multi-parametric syndromes. Susceptibility to stress and depression is individually different. The best animal model of individual differences that can be used to study the neurobiology of affect regards spontaneous reactions to novelty. Experimentally, when naive rats are exposed to the stress of a novel environment, they display a highly variable exploratory activity and are classified as high or low responders (HR or LR, respectively). Importantly, HR and LR rats do not seem to exhibit a substantial differentiation in relation to their 'depressive-like' status in the forced swim test (FST), a widely used animal model of 'behavioral despair'. In the present study, we investigated whether FST exposure would be accompanied by phenotype-dependent differences in hippocampal gene expression in HR and LR rats.ResultsHR and LR rats present a distinct behavioral pattern in the pre-test session but develop comparable depressive-like status in the second FST session. At 24 h following the second FST session, HR and LR rats (stressed and unstressed controls) were sacrificed and hippocampal samples were independently analyzed on whole rat genome Illumina arrays. Functional analysis into pathways and networks was performed using Ingenuity Pathway Analysis (IPA) software. Notably, hippocampal gene expression signatures between HR and LR rats were markedly divergent, despite their comparable depressive-like status in the FST. These molecular differences are reflected in both the extent of transcriptional remodeling (number of significantly changed genes) and the types of molecular pathways affected following FST exposure. A markedly higher number of genes (i.e., 2.28-fold) were statistically significantly changed following FST in LR rats, as compared to their HR counterparts. Notably, genes associated with neurogenesis and synaptic plasticity were induced in the hippocampus of LR rats in response to FST, whereas in HR rats, FST induced pathways directly or indirectly associated with induction of apoptotic mechanisms.ConclusionsThe markedly divergent gene expression signatures exposed herein support the notion that the hippocampus of HR and LR rats undergoes distinct transcriptional remodeling in response to the same stress regimen, thus yielding a different FST-related 'endophenotype', despite the seemingly similar depressive-like phenotype.
| S-EPMC3941591 | biostudies-literature
Project description:PurposeWe developed a method for quantifying intraoperative torsional forced ductions and validated the new test by comparing patients with oblique dysfunction and controls.DesignComparative case series.SubjectsWe studied 33 eyes with oblique dysfunction (9 with presumed congenital superior oblique palsy [SOP], 13 with acquired SOP, 7 with Brown syndrome, and 4 with inverted Brown syndrome) and 31 controls. We also studied 6 eyes after superior oblique (SO) disinsertion and 2 eyes after inferior oblique (IO) disinsertion.MethodsUnder deep general anesthesia, the 12 and 6 o'clock positions at the limbus were marked and the globe was maximally excyclorotated and incyclorotated without retroplacement until the first resistance was felt, and the angle of rotation (in degrees) was read on a Mendez ring by the surgeon. A photograph was taken in each position to be read by a masked observer.Main outcome measuresMaximal excyclorotation and maximal incyclorotation in each oblique dysfunction and in controls by both surgeon's report and photographic assessment. We duplicated the photographs to evaluate test-retest reliability and to evaluate agreement between the surgeon's assessments and the photographic assessment.ResultsSurgeon's assessment revealed greater maximal excyclorotation in eyes with presumed congenital SOP than in controls (median, 40 vs. 30 degrees). Maximal excyclorotation in eyes with acquired SOP was similar to that in controls (30 degrees in both). Eyes with Brown syndrome and inverted Brown syndrome had lower maximal excyclorotation than in controls (10 and 20 vs. 30 degrees, respectively). Maximal incyclorotation in eyes with inverted Brown syndrome was lower than in controls (12.5 vs. 30 degrees), whereas it was similar to that of controls in eyes with presumed congenital SOP, acquired SOP, and Brown syndrome (30 degrees in each condition). Median maximal excyclorotation after SO disinsertion was 62.5 degrees, and maximal incyclorotation after IO disinsertion was 60 degrees. Photographic assessment yielded findings essentially identical to the surgeon's report. Test-retest reliability of the photographic reading was excellent, and agreement between the surgeon's report and the photographic reading was also excellent (95% limits of agreement, 4.4 and 11.6; intraclass correlation coefficient, 0.97 and 0.82, respectively).ConclusionsThe new torsional forced duction test enables quantitative assessment of SO and IO tightness and laxity.
| S-EPMC4549184 | biostudies-literature
Project description:Individual differences in coping with stress may determine either a vulnerable or resilient phenotype. Therefore, it is important to better understand the biology underlying the behavioral phenotype. We assessed whether individual behavioral phenotype to acute stress is related with the hippocampal expression of glucocorticoid receptor (GR), Nurr1, interleukin-1 beta (IL-1β) or brain-derived neurotrophic factor (BDNF). Wistar male rats were exposed to forced swimming for 15 min and sacrificed at different times. Behavioral response was analyzed, and it was compared with the gene and protein expression of GR, Nurr1, IL-1β and BDNF in the hippocampus for each time point. Behavioral phenotyping showed a group with high immobility (vulnerable) while another had low immobility (resilient). No significant differences were found in the Nurr1, IL-1β and BDNF mRNA levels between resilient and vulnerable rats at different recovery times except for Nr3c1 (gene for GR). However, exposure to stress caused significantly higher levels of GR, Nurr1 and IL-1β proteins of vulnerable compared to resilient rats. This variability of behavioral phenotypes is associated with a differential molecular response to stress that involves GR, Nurr1, and IL-1β as mediators in coping with stress. This contributes to identifying biomarkers of susceptibility to stress.
| S-EPMC8657438 | biostudies-literature
Project description:Rats were anesthetized with sodium pentobarbital (50 mg/kg, i.p.) and placed in a stereotaxic instrument (Kopf instrument). After exposing the skull, bilateral craniotomy (0.5 - 0.8 mm holes, 4 mm posterior to bregma and 2.6 mm lateral from midline) was done. In one group of rats (Lactate group), each hippocampus (3.5 mm ventral from the surface of the skull at the craniotomy site) was infused with 100 nmol of L-lactate dissolved in 1µl of ACSF at a flow rate of 0.1 µl/min (controlled by microinjection pump; World Precision Instruments, USA). In another group of rats (ACSF group), 1 µl of artificial cerebrospinal fluid (ACSF; NaCl 124 mM, KCl 3 mM, CaCl2 2.4 mM, MgSO4 1.3 mM, glucose 10 mM, and HEPES 10 mM, pH = 7.3) was infused per HPC. Needle was kept at injection site for additional 5 minutes for the proper dispersion of solution after L-lactate/ACSF infusion. Then rats were kept into their cages for approximately 60 minutes. After that higher dose of sodium pentobarbital was given, and decapitation was done quickly. Following decapitation, the dura mater was removed carefully, and the brain was flipped out from skull into ice cold PBS using spatula. The right and left hippocampus were isolated on an ice-cold plate using sterile forceps and were stored immediately at -80°C until further use. Later, the right hippocampus was used as sample for mass spectrometry (MS).
2023-02-23 | PXD039121 | JPOST Repository
Project description:A fundamental issue in locomotion is to understand how muscle forcing produces apparently complex deformation kinematics leading to movement of animals like undulatory swimmers. The question of whether complicated muscle forcing is required to create the observed deformation kinematics is central to the understanding of how animals control movement. In this work, a forced damped oscillation framework is applied to a chain-link model for undulatory swimming to understand how forcing leads to deformation and movement. A unified understanding of swimming, caused by muscle contractions ("active" swimming) or by forces imparted by the surrounding fluid ("passive" swimming), is obtained. We show that the forcing triggers the first few deformation modes of the body, which in turn cause the translational motion. We show that relatively simple forcing patterns can trigger seemingly complex deformation kinematics that lead to movement. For given muscle activation, the forcing frequency relative to the natural frequency of the damped oscillator is important for the emergent deformation characteristics of the body. The proposed approach also leads to a qualitative understanding of optimal deformation kinematics for fast swimming. These results, based on a chain-link model of swimming, are confirmed by fully resolved computational fluid dynamics (CFD) simulations. Prior results from the literature on the optimal value of stiffness for maximum speed are explained.
| S-EPMC3681642 | biostudies-literature
Project description:Many immediate early genes (IEGs) have activity-dependent induction in a subset of brain subdivisions or neuron types. However, none have been reported yet with regulation specific to thalamic-recipient sensory neurons of the telencephalon or in the thalamic sensory input neurons themselves. Here, we report the first such gene, dual specificity phosphatase 1 (dusp1). Dusp1 is an inactivator of mitogen-activated protein kinase (MAPK), and MAPK activates expression of egr1, one of the most commonly studied IEGs, as determined in cultured cells. We found that in the brain of naturally behaving songbirds and other avian species, hearing song, seeing visual stimuli, or performing motor behavior caused high dusp1 upregulation, respectively, in auditory, visual, and somatosensory input cell populations of the thalamus and thalamic-recipient sensory neurons of the telencephalic pallium, whereas high egr1 upregulation occurred only in subsequently connected secondary and tertiary sensory neuronal populations of these same pathways. Motor behavior did not induce high levels of dusp1 expression in the motor-associated areas adjacent to song nuclei, where egr1 is upregulated in response to movement. Our analysis of dusp1 expression in mouse brain suggests similar regulation in the sensory input neurons of the thalamus and thalamic-recipient layer IV and VI neurons of the cortex. These findings suggest that dusp1 has specialized regulation to sensory input neurons of the thalamus and telencephalon; they further suggest that this regulation may serve to attenuate stimulus-induced expression of egr1 and other IEGs, leading to unique molecular properties of forebrain sensory input neurons.
| S-EPMC2904818 | biostudies-literature