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Individual stress vulnerability is predicted by short-term memory and AMPA receptor subunit ratio in the hippocampus.

ABSTRACT: Increased vulnerability to aversive experiences is one of the main risk factors for stress-related psychiatric disorders as major depression. However, the molecular bases of vulnerability, on the one hand, and stress resilience, on the other hand, are still not understood. Increasing clinical and preclinical evidence suggests a central involvement of the glutamatergic system in the pathogenesis of major depression. Using a mouse paradigm, modeling increased stress vulnerability and depression-like symptoms in a genetically diverse outbred strain, and we tested the hypothesis that differences in AMPA receptor function may be linked to individual variations in stress vulnerability. Vulnerable and resilient animals differed significantly in their dorsal hippocampal AMPA receptor expression and AMPA receptor binding. Treatment with an AMPA receptor potentiator during the stress exposure prevented the lasting effects of chronic social stress exposure on physiological, neuroendocrine, and behavioral parameters. In addition, spatial short-term memory, an AMPA receptor-dependent behavior, was found to be predictive of individual stress vulnerability and response to AMPA potentiator treatment. Finally, we provide evidence that genetic variations in the AMPA receptor subunit GluR1 are linked to the vulnerable phenotype. Therefore, we propose genetic variations in the AMPA receptor system to shape individual stress vulnerability. Those individual differences can be predicted by the assessment of short-term memory, thereby opening up the possibility for a specific treatment by enhancing AMPA receptor function.

SUBMITTER: Schmidt MV

PROVIDER: S-EPMC6634917 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Individual stress vulnerability is predicted by short-term memory and AMPA receptor subunit ratio in the hippocampus.

Schmidt Mathias V MV Trümbach Dietrich D Weber Peter P Wagner Klaus K Scharf Sebastian H SH Liebl Claudia C Datson Nicole N Namendorf Christian C Gerlach Tamara T Kühne Claudia C Uhr Manfred M Deussing Jan M JM Wurst Wolfgang W Binder Elisabeth B EB Holsboer Florian F Müller Marianne B MB

The Journal of neuroscience : the official journal of the Society for Neuroscience 20101201 50

Increased vulnerability to aversive experiences is one of the main risk factors for stress-related psychiatric disorders as major depression. However, the molecular bases of vulnerability, on the one hand, and stress resilience, on the other hand, are still not understood. Increasing clinical and preclinical evidence suggests a central involvement of the glutamatergic system in the pathogenesis of major depression. Using a mouse paradigm, modeling increased stress vulnerability and depression-li ...[more]

PMID: 21159965

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Project description:ObjectiveThe aim of this study was to explore the predictive value of the ratio of procalcitonin (PCT) in serum to Simpson's dominance index (SDI) in bronchoalveolar lavage fluid (BALF), in short-term prognosis of patients with severe bacterial pneumonia (SBP).MethodsThis is a retrospective review of case materials of 110 patients with SBP who selected BALF metagenomic next-generation sequencing technique in the intensive care unit (ICU) of the Affiliated Hospital of Yangzhou University from January 2019 and July 2022. Based on the acute physiology and chronic health status score II, within 24 h after admission to the ICU, patients were divided into a non-critical group (n = 40) and a critical group (n = 70). Taking death caused by bacterial pneumonia as the endpoint event, the 28-day prognosis was recorded, and the patients were divided into a survival group (n = 76) and a death group (n = 34). The SDI, PCT, C-reactive protein (CRP), PCT/SDI, and CRP/SDI were compared and analyzed.ResultsCompared with the non-critical group, the critical group had a higher PCT level, a greater PCT/SDI ratio, a longer ventilator-assisted ventilation time (VAVT), and more deaths in 28 days. Compared with the survivors, the death group had a higher PCT level, a lower SDI level, and a greater PCT/SDI ratio. The SDI level was significantly negatively correlated with the VAVT (r = -0.675, p < 0.05), while the PCT level, ratio of PCT/SDI, and ratio of CRP/SDI were remarkably positively correlated with VAVT (r = 0.669, 0.749, and 0.718, respectively, p < 0.05). The receiver operating characteristic (ROC) curves analysis showed that the area under ROC curves of PCT/SDI predicting patient death within 28 days was 0.851, followed by PCT + SDI, PCT, SDI, and CRP/SDI (0.845, 0.811, 0.778, and 0.720, respectively). The sensitivity and specificity of PCT/SDI for predicting death were 94.1% and 65.8%, respectively, at the optimal value (11.56). Cox regression analysis displayed that PCT/SDI (HR = 1.562; 95% CI: 1.271 to 1.920; p = 0.039) and PCT (HR = 1.148; 95% CI: 1.105 to 1.314; p = 0.015) were independent predictors of death in patients.ConclusionThe ratio of PCT/SDI was a more valuable marker in predicting the 28-day prognosis in patients with SBP.

Dataset Information

Individual stress vulnerability is predicted by short-term memory and AMPA receptor subunit ratio in the hippocampus.

Publications

Individual stress vulnerability is predicted by short-term memory and AMPA receptor subunit ratio in the hippocampus.

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