scholarly journals Social Instability is an Effective Chronic Stress Paradigm for both Male and Female Mice

2019 ◽  
Author(s):  
Christine N. Yohn ◽  
Sandra A. Ashamalla ◽  
Leshya Bokka ◽  
Mark M. Gergues ◽  
Alexander Garino ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Hpa Axis ◽  
Social Stress ◽  
Antidepressant Treatment ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Social Instability ◽  
Female Mice ◽  
Negative Valence ◽  
Males And Females

ABSTRACTDespite stress-associated disorders having a higher incidence rate in females, preclinical research mainly focuses on males. Chronic stress paradigms, such as chronic social defeat and chronic corticosterone administration, were mainly designed and validated in males and subsequent attempts to use these paradigms in females has demonstrated sex differences in the behavioral and HPA axis response to stress. Here, we developed a social stress paradigm, social instability stress (SIS), which exposes adult mice to unstable social hierarchies for 7 weeks. SIS effectively induces negative valence behaviors and hypothalamus-pituitary-adrenal (HPA) axis activation in both males and females. Importantly, while there were effects of estrous cycle on behavior, this variability did not impact the overall effects of SIS on behavior, suggesting estrous does not need to be tracked while utilizing SIS. Furthermore, the effects of SIS on negative valence behaviors were also reversed following chronic antidepressant treatment with fluoxetine (FLX) in both males and females. SIS also reduced adult hippocampal neurogenesis in female mice, while chronic FLX treatment increased adult hippocampal neurogenesis in both males and females. Overall, these data demonstrate that the SIS paradigm is an ethologically valid approach that effectively induces chronic stress in both adult male and adult female mice.

scholarly journals Fluoxetine effects on behavior and adult hippocampal neurogenesis in female C57BL/6J mice across the estrous cycle

2018 ◽  
Author(s):  
Christine N. Yohn ◽  
Sophie Shifman ◽  
Alexander Garino ◽  
Emma Diethorn ◽  
Leshya Bokka ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Antidepressant Treatment ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
List Type ◽  
Female Mice ◽  
Chronic Fluoxetine ◽  
Brain And Behavior ◽  
And Behavior ◽  
The Impact

AbstractSome mood disorders, such as major depressive disorder, are more prevalent in women than in men. However, historically preclinical studies in rodents have a lower inclusion rate of females than males, possibly due to the fact that behavior can be affected by the estrous cycle. Several studies have demonstrated that chronic antidepressant treatment can decrease anxiety-like behaviors and increase adult hippocampal neurogenesis in male rodents. However, very few studies have conclusively looked at the effects of antidepressants on behavior and neurogenesis across the estrous cycle in naturally cycling female rodents. Here we analyze the effects of chronic treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac) on behavior and adult hippocampal neurogenesis in naturally cycling C57BL/6J females across all four phases of the estrous cycle. Interestingly, we find that the effects of fluoxetine on both behavior and adult hippocampal neurogenesis are driven by mice specifically in the estrus or diestrus phases of the estrous cycle. Taken together our data is the first to illustrate the impact of fluoxetine on brain and behavior across all four stages of the murine estrous cycle.HighlightsChronic fluoxetine reduces anxiety-like behaviors in naturally cycling female miceChronic fluoxetine increases adult hippocampal neurogenesis in naturally cycling female miceThe effects of chronic fluoxetine on behavior and adult hippocampal neurogenesis are driven by the estrus and diestrus phases of the estrous cycle

scholarly journals A non-linear relation between levels of adult hippocampal neurogenesis and expression of the immature neuron marker doublecortin

2020 ◽  
Author(s):  
Indira Mendez-David ◽  
Denis J David ◽  
Claudine Deloménie ◽  
Jean-Martin Beaulieu ◽  
Alain M. Gardier ◽  
...  
Keyword(s):  
Mouse Model ◽  
Chronic Stress ◽  
Granule Cells ◽  
Antidepressant Treatment ◽  
Hippocampal Neurogenesis ◽  
Neural Progenitors ◽  
Adult Hippocampal Neurogenesis ◽  
List Type ◽  
Stress Model ◽  
Immature Neuron

ABSTRACTWe investigated the mechanisms underlying the effects of the antidepressant fluoxetine on behavior and adult hippocampal neurogenesis (AHN). After confirming our earlier report that the signaling molecule β2-arrestin is required for the antidepressant-like effects of fluoxetine, we found that the effects of fluoxetine on proliferation of neural progenitors and on survival of adult-born granule cells are absent in the β2-arrestin knockout (β2-Arr KO) mice. To our surprise fluoxetine induced a dramatic upregulation of doublecortin (DCX) in the β2-Arr KO mice, indicating that DCX expression can be increased even though AHN is not. We discovered two other conditions where DCX expression is regulated non linearly compared to levels of AHN: a chronic stress model where DCX is upregulated and an inflammation model where DCX is down regulated. We conclude that assessing DCX expression alone to quantify levels of AHN can be misleading and that caution should be applied when label retention techniques are not available.HIGHLIGHTSβ2-arrestin (β-Arr2) is required for the antidepressant-like effects of fluoxetine.A dramatic upregulation of doublecortin (DCX) is observed in the β2-Arr KO mice after antidepressant treatment whereas its effects on proliferation of neural progenitors and on survival of adult-born granule cells are absent.DCX is more upregulated than the number of young neurons in a mouse model of depression.DCX is more down regulated than the number of young neurons in a model of inflammation.microRNAs (miRs) may contribute to the regulation of DCX mRNA expression.

scholarly journals Selective activation of estrogen receptors α and β: Implications for depressive-like phenotypes in female mice exposed to chronic unpredictable stress

2019 ◽  
Author(s):  
Rand S. Eid ◽  
Stephanie E. Lieblich ◽  
Paula Duarte-Guterman ◽  
Jessica A. Chaiton ◽  
Amanda G. Mah ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Hpa Axis ◽  
Dorsal Hippocampus ◽  
Tail Suspension Test ◽  
Hippocampal Neurogenesis ◽  
Stress Conditions ◽  
Adult Hippocampal Neurogenesis ◽  
Estrogen Signaling ◽  
Chronic Unpredictable Stress ◽  
17Β Estradiol

AbstractThe estrogen receptor (ER) mechanisms by which 17β-estradiol influences depressive-like behaviour have primarily been investigated acutely and not within an animal model of depression. Therefore, the current study aimed to dissect the contribution of ERα and ERβ to the effects of 17β-estradiol under non-stress and chronic stress conditions. Ovariectomized (OVX) or sham-operated mice were treated chronically (47 days) with 17β-estradiol (E2), the ERβ agonist diarylpropionitrile (DPN), the ERα agonist propylpyrazole-triol (PPT), or vehicle. On day 15 of treatment, mice from each group were assigned to Chronic Unpredictable Stress (CUS; 28 days) or non-CUS conditions. Mice were assessed for anxiety- and depressive-like behaviour and hypothalamic-pituitary-adrenal (HPA) axis function. Cytokine and chemokine levels, and postsynaptic density protein 95 were measured in the hippocampus and frontal cortex, and adult hippocampal neurogenesis was assessed. Overall, the effects of CUS were more robust that those of estrogenic treatments, as seen by increased immobility in the tail suspension test (TST), reduced PSD-95 expression, reduced neurogenesis in the ventral hippocampus, and HPA axis negative feedback dysregulation. However, we also observe CUS-dependent and -independent effects of ovarian status and estrogenic treatments. The effects of CUS on PSD-95 expression, the cytokine milieu, and in TST were largely driven by PPT and DPN, indicating that these treatments were not protective. Independent of CUS, estradiol increased neurogenesis in the dorsal hippocampus, blunted the corticosterone response to an acute stressor, but increased anxiety-like behaviour. These findings provide insights into the complexities of estrogen signaling in modulating depressive-like phenotypes under non-stress and chronic stress conditions.

Sexual activity counteracts the suppressive effects of chronic stress on adult hippocampal neurogenesis and recognition memory

2013 ◽  
Vol 1538 ◽  
pp. 26-40 ◽  
Author(s):  
Jong-In Kim ◽  
Jae Won Lee ◽  
Young Ah Lee ◽  
Dong-Hun Lee ◽  
Nam Soo Han ◽  
...  
Keyword(s):  
Recognition Memory ◽  
Sexual Activity ◽  
Chronic Stress ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis

FC29-02 - Is prenatal exposure to alcohol a factor which re-program the brain?

2011 ◽  
Vol 26 (S2) ◽  
pp. 1978-1978
Author(s):  
J.H. Sliwowska
Keyword(s):  
Prenatal Exposure ◽  
Hpa Axis ◽  
Alcohol Exposure ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Ovariectomized Rats ◽  
List Type ◽  
Depression And Anxiety ◽  
Hpg Axis ◽  
The Brain

IntroductionFetal programming refers to the concept that early environmental factors, including prenatal exposure to stress and drugs, can permanently organize or imprint physiological and behavioural systems and increase vulnerability to disorders such as depression and anxiety later in life.AimsIs prenatal exposure to alcohol a factor which re-programs the brain?ObjectivesEffects of prenatal alcohol exposure (PAE) on:1)the hypothalamus-pituitary-adrenal (HPA) axis;2)the hypothalamus-pituitary-gonadal (HPG) axis;3)serotonergic (5-HT) system and4)adult hippocampal neurogenesis are presented.MethodsOffspring from prenatal ethanol (PAE), pair-fed (PF) and ad lib-fed control (C) dams are studied across the development or in adulthood. Immunocytochemistry and in situ hybridization techniques are used.ResultsIn term of the HPA axis: PAE alters the balance of mineralocorticoids/glucocorticoids (MRs/GRs) receptor levels in the hippocampus of adult females. In the case of the HPG axis: PAE delays puberty and changes hormonal profiles in males and females. PAE also decreases numbers of 5-HT-immunoreactive neurons in the dorsal raphe nucleus of the brainstem in ovariectomized rats and estradiol and progesterone modulate those effects. Finally, in adult PAE males, but not females stress-induced decrease in neurogenesis is altered.ConclusionsIn our animal model PAE re-programs the brain. Effects of PAE are long-lasting, affect HPA and HPG axes, 5-HT system and adult hippocampal neurogenesis and if seen in humans could contribute to increased vulnerability to depression and anxiety.

scholarly journals Social instability is an effective chronic stress paradigm for both male and female mice

2019 ◽  
Vol 160 ◽  
pp. 107780 ◽  
Author(s):  
Christine N. Yohn ◽  
Sandra A. Ashamalla ◽  
Leshya Bokka ◽  
Mark M. Gergues ◽  
Alexander Garino ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Male And Female ◽  
Social Instability ◽  
Female Mice

Adult Hippocampal Neurogenesis Protects From Chronic Stress Effects in Mice

2020 ◽  
Vol 87 (9) ◽  
pp. S58-S59
Author(s):  
Christoph Anacker ◽  
Victor Luna ◽  
Ryan Shores ◽  
Gregory Stevens ◽  
Rene Hen
Keyword(s):  
Chronic Stress ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Stress Effects

scholarly journals Chronic corticosterone administration induces negative valence and impairs positive valence behaviors in mice

2019 ◽  
Author(s):  
Andrew Dieterich ◽  
Prachi Srivastava ◽  
Aitesam Sharif ◽  
Karina Stech ◽  
Benjamin A. Samuels
Keyword(s):  
Negative Affect ◽  
Mood Disorders ◽  
Chronic Stress ◽  
Antidepressant Treatment ◽  
Reward Processing ◽  
Pharmacological Stress ◽  
Potential Threat ◽  
Impaired Performance ◽  
Negative Valence ◽  
Positive Valence

AbstractBehavioral approaches utilizing rodents to study mood disorders have focused primarily on negative valence behaviors associated with potential threat (anxiety). However, for disorders such as depression, positive valence behaviors that assess reward processing may be more translationally-valid and predictive of antidepressant treatment outcome. Chronic corticosterone (CORT) administration is a well-validated pharmacological stressor that increases negative valence behaviors (David et al., 2009; Gourley et al., 2008a,b; Gourley et al., 2012; Olausson et al., 2013). However, whether chronic stress paradigms such as CORT administration also lead to deficits in positive valence behaviors remains unclear. We treated male C57BL/6J mice with chronic CORT and assessed both negative and positive valence behaviors. We found that CORT induced negative valence behaviors associated with anxiety in the open field and NSF. Interestingly, CORT also impaired instrumental acquisition, reduced sensitivity to a devalued outcome, reduced breakpoint in progressive ratio, and impaired performance in probabilistic reversal learning. Taken together, these results demonstrate that chronic CORT administration at the same dosage both induces negative valence behaviors associated with anxiety and impairs positive valence behaviors associated with reward processing. These data suggest that CORT administration is a useful experimental system for preclinical approaches to studying stress-induced mood disorders.Significance StatementChronic exposure to stress can precipitate mood disorders such as anxiety and depression. However, most studies focus on the effects of chronic stress on increasing negative affect behaviors. Elucidating how chronic stress impacts translationally-valid positive valence behaviors is less studied. Here, we show that chronic pharmacological stress induces negative affect behaviors associates with anxiety and impairs reward-related, positive valence behaviors in mice.

scholarly journals Inhibiting adult neurogenesis differentially affects spatial learning in females and males

2021 ◽  
Author(s):  
Timothy P O'Leary ◽  
Baran Askari ◽  
Bonnie Lee ◽  
Kathryn Darby ◽  
Cypress Knudson ◽  
...  
Keyword(s):  
Sex Differences ◽  
Search Strategy ◽  
Cold Water ◽  
Mossy Fiber ◽  
Dorsal Hippocampus ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Early Gene ◽  
Males And Females ◽  
Adult Born Neurons

Adult hippocampal neurogenesis has been implicated in the spatial processing functions of the hippocampus but ablating neurogenesis does not consistently lead to behavioral deficits in spatial tasks. Parallel studies have shown that adult-born neurons also regulate behavioral responses to stressful and aversive stimuli. We therefore hypothesized that spatial functions of adult-born neurons may be more prominent under conditions of stress, and may differ between males and females given established sex differences in stress responding. To test this we trained intact and neurogenesis-deficient rats in the spatial water maze at temperatures that vary in their degree of aversiveness. At standard temperatures (25°C) ablating neurogenesis did not alter learning and memory in either sex, consistent with prior work. However, in cold water (16°C), ablating neurogenesis had divergent sex-dependent effects: relative to intact rats, male neurogenesis-deficient rats were slower to escape and female neurogenesis-deficient rats were faster. Neurogenesis promoted temperature-related changes in search strategy in females, but it promoted search strategy stability in males. Females displayed greater recruitment of the dorsal hippocampus than males, particularly at 16°C. However, blocking neurogenesis did not alter activity-dependent immediate-early gene expression in either sex. Finally, morphological analyses of retrovirally-labelled neurons revealed greater experience-dependent plasticity in new neurons in males. Neurons had comparable morphology in untrained rats but 16°C training increased spine density, and 25°C training caused shrinkage of mossy fiber presynaptic terminals, specifically in males. Collectively, these findings indicate that neurogenesis functions in memory are prominent under conditions of stress, they provide the first evidence for sex differences in the behavioral function of newborn neurons, and they suggest possibly distinct roles for neurogenesis in cognition and mental health in males and females.

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