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Quantitative analysis of Gria1, Gria2, Dlg1 and Dlg4 expression levels in hippocampus following forced swim stress in mice.

ABSTRACT: AMPA receptors and interacting proteins are importantly involved in mediating stress-dependent plasticity. Previously we reported that GluA1-containing AMPA receptors and their interaction with PDZ-proteins are required for the experience-dependent expression of behavioral despair in the forced swim test. However, it is unclear if the expression of GluA1-containing AMPA receptors is affected by this type of behavior. Here we investigated in wild type mice, whether hippocampal gene or protein levels of GluA1 or associated PDZ proteins is altered following forced swim stress. We show that expression of Dlg4 (the gene coding for PSD-95) was strongly reduced after two days of forced swimming. In contrast, levels of Dlg1, Gria1, and Gria2 (coding for SAP97, GluA1, and GluA2 respectively) were not affected after one or two days of forced swimming. The changes in gene expression largely did not translate to the protein level. These findings indicate a limited acute effect of forced swim stress on the expression of the investigated targets and suggest that the acute involvement of GluA1-containing AMPA receptors tor forced swim behavior is a result of non-genomic mechanisms.

SUBMITTER: Freudenberg F

PROVIDER: S-EPMC6773768 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Quantitative analysis of Gria1, Gria2, Dlg1 and Dlg4 expression levels in hippocampus following forced swim stress in mice.

Freudenberg Florian F

Scientific reports 20191001 1

AMPA receptors and interacting proteins are importantly involved in mediating stress-dependent plasticity. Previously we reported that GluA1-containing AMPA receptors and their interaction with PDZ-proteins are required for the experience-dependent expression of behavioral despair in the forced swim test. However, it is unclear if the expression of GluA1-containing AMPA receptors is affected by this type of behavior. Here we investigated in wild type mice, whether hippocampal gene or protein lev ...[more]

PMID: 31575955

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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.

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.

Dataset Information

Quantitative analysis of Gria1, Gria2, Dlg1 and Dlg4 expression levels in hippocampus following forced swim stress in mice.

Publications

Quantitative analysis of Gria1, Gria2, Dlg1 and Dlg4 expression levels in hippocampus following forced swim stress in mice.

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