Differences in FKBP51 Regulation Following Chronic Social Defeat Stress Correlate with Individual Stress Sensitivity: Influence of Paroxetine Treatment

Wagner, Klaus V.; Marinescu, Daria; Hartmann, Jakob; Wang, Xiao-Dong; Labermaier, Christiana; Scharf, Sebastian H.; Liebl, C.; Uhr, Manfred; Holsboer, Florian; Müller, Marianne B.; Schmidt, Mathias V.

doi:10.1038/npp.2012.150

Cited by 55 publications

(47 citation statements)

References 52 publications

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“…Likewise, in aged adult offspring, there was an upregulation of Fkbp5 gene expression in the PVN and ARC nuclei following CSDS on account of exposure to maternal obesity. Previous rodent studies have nicely illustrated that Fkbp5 expression is increased in select brain regions on account of both acute and chronic stress exposure [48,49]. The parallel effects of stress exposure and maternal dietary condition on Fkbp5 gene expression may contribute to the paralleled effects of CSDS and maternal diet on stress coping and anxiety-like behaviors reported here.…”

Section: Discussionsupporting

confidence: 63%

Prenatal Exposure to Maternal Obesity Alters Anxiety and Stress Coping Behaviors in Aged Mice

et al. 2015

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Background: There is growing evidence that maternal obesity and prenatal exposure to a high-fat diet program fetal development to regulate the physiology and behavior of the offspring in adulthood. Yet the extent to which the maternal dietary environment contributes to adult disease vulnerability remains unclear. In the current study we tested whether prenatal exposure to maternal obesity increases the offspring's vulnerability to stress-related psychiatric disorders. Methods: We used a mouse model of maternal diet-induced obesity to investigate whether maternal obesity affects the response to adult chronic stress exposure in young adult (3-month-old) and aged adult (12-month-old) offspring. Results: Long-lasting, delayed impairments to anxiety-like behaviors and stress coping strategies resulted on account of prenatal exposure to maternal obesity. Although maternal obesity did not change the offspring's behavioral response to chronic stress per se, we demonstrate that the behavioral outcomes induced by prenatal exposure to maternal obesity parallel the deleterious effects of adult chronic stress exposure in aged male mice. We found that the glucocorticoid receptor (GR, Nr3c1) is upregulated in various hypothalamic nuclei on account of maternal obesity. In addition, gene expression of a known regulator of the GR, FKBP51, is increased specifically within the paraventricular nucleus. Conclusions: These findings indicate that maternal obesity parallels the deleterious effects of adult chronic stress exposure, and furthermore identifies GR/FKBP51 signaling as a novel candidate pathway regulated by maternal obesity.

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Section: Discussionsupporting

confidence: 63%

Prenatal Exposure to Maternal Obesity Alters Anxiety and Stress Coping Behaviors in Aged Mice

et al. 2015

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“…All tests were described and validated previously Wagner et al, 2012;Malkesman et al, 2010). Tests were recorded and analyzed using the video tracking software ANY-maze (ANY-maze 4.20, Stoelting, IL).…”

Section: Behavioral Testingmentioning

confidence: 99%

“…Preparation of membrane fractions and Co-IP analysis was performed as described previously (Wagner et al, 2013;Wagner et al, 2012). In short, membrane fractions were isolated using the Calbiochem Proteoextract kit (EMD Biosciences), protein concentration was determined, and 1.2 mg of lysate was incubated with 2.5 mg mGluR5 antibody (Millipore) overnight at 4 1C.…”

Section: Co-immunoprecipitationmentioning

confidence: 99%

Homer1/mGluR5 Activity Moderates Vulnerability to Chronic Social Stress

Wagner

Hartmann

Labermaier

et al. 2014

Neuropsychopharmacol

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Stress-induced psychiatric disorders, such as depression, have recently been linked to changes in glutamate transmission in the central nervous system. Glutamate signaling is mediated by a range of receptors, including metabotropic glutamate receptors (mGluRs). In particular, mGluR subtype 5 (mGluR5) is highly implicated in stress-induced psychopathology. The major scaffold protein Homer1 critically interacts with mGluR5 and has also been linked to several psychopathologies. Yet, the specific role of Homer1 in this context remains poorly understood. We used chronic social defeat stress as an established animal model of depression and investigated changes in transcription of Homer1a and Homer1b/c isoforms and functional coupling of Homer1 to mGluR5. Next, we investigated the consequences of Homer1 deletion, overexpression of Homer1a, and chronic administration of the mGluR5 inverse agonist CTEP (2-chloro-4-((2,5-dimethyl-1-(4-(trifluoromethoxy)phenyl)-1H-imidazol-4-yl)ethynyl)pyridine) on the effects of chronic stress. In mice exposed to chronic stress, Homer1b/c, but not Homer1a, mRNA was upregulated and, accordingly, Homer1/mGluR5 coupling was disrupted. We found a marked hyperactivity behavior as well as a dysregulated hypothalamic-pituitary-adrenal axis activity in chronically stressed Homer1 knockout (KO) mice. Chronic administration of the selective and orally bioavailable mGluR5 inverse agonist, CTEP, was able to recover behavioral alterations induced by chronic stress, whereas overexpression of Homer1a in the hippocampus led to an increased vulnerability to chronic stress, reflected in an increased physiological response to stress as well as enhanced depression-like behavior. Overall, our results implicate the glutamatergic system in the emergence of stress-induced psychiatric disorders, and support the Homer1/mGluR5 complex as a target for the development of novel antidepressant agents.

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“…There is an emerging body of research examining biological markers for resilience, including glucocorticoid receptors (Wagner, Marinescu et al 2012) and neuropeptides (Kozlovsky, Matar et al 2009, Cohen, Liu et al 2012). …”

Section: Resilience and Depressionmentioning

confidence: 99%

The effect of strategies of personal resilience on depression recovery in an Australian cohort: A mixed methods study

et al. 2014

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Strategies of personal resilience enable successful adaptation in adversity. Among patients experiencing depression symptoms, we explored which personal resilience strategies they find most helpful and tested the hypothesis that use of these strategies improves depression recovery. We used interview and survey data from the Diagnosis, Management and Outcomes of Depression in Primary Care 2005 cohort of patients experiencing depression symptoms in Victoria, Australia. A total of 564 participants answered a computer-assisted telephone interview question at 12 months follow-up, about what they found most helpful for their depression, stress or worries. Depressive disorder and severity were measured at annual follow-up using the Composite International Diagnostic Interview and the Patient Health Questionnaire self-rating questionnaire. Using interview responses, we categorised participants as users or not of

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Differences in FKBP51 Regulation Following Chronic Social Defeat Stress Correlate with Individual Stress Sensitivity: Influence of Paroxetine Treatment

Cited by 55 publications

References 52 publications

Prenatal Exposure to Maternal Obesity Alters Anxiety and Stress Coping Behaviors in Aged Mice

Prenatal Exposure to Maternal Obesity Alters Anxiety and Stress Coping Behaviors in Aged Mice

Homer1/mGluR5 Activity Moderates Vulnerability to Chronic Social Stress

The effect of strategies of personal resilience on depression recovery in an Australian cohort: A mixed methods study

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