Sex differences in sleep, anhedonia, and HPA axis activity in a rat model of chronic social defeat

AbstractHair glucocorticoids are increasingly popular biomarkers, used across numerous research fields as a measure of stress. Although they are suggested to be a proxy of the average HPA axis activity spanning a period of weeks or months into the past, this theory has never been tested.In the present study, adrenalectomized rats with no endogenous (adrenal) glucocorticoid production were used to study how circulating glucocorticoid levels would be reflected in the glucocorticoid levels found in hair samples. By dosing the animals daily with high levels of corticosterone for seven days, while sampling hairs before, during, and after treatments, a timeline for glucocorticoid uptake into hairs was constructed. This kinetic profile was compared to two hypothetical models, and the theory that hair glucocorticoids are a record of historical stress had to be rejected.Corticosterone concentrations in hairs were found to increase within three hours of the first injection, the highest concentrations were found on the seventh day of treatments, and the decrease in concentrations post-treatment suggests rapid elimination. We speculate that hair glucocorticoid levels can only be used to characterize a stress-response for a few days following a postulated stressor.An updated model, where glucocorticoids diffuse into, along, and out of hairs needs to be adopted to reconcile the experimentally obtained data. The inescapable consequence of this updated model is that hair glucocorticoids become a marker of – and can only be used to study – recent, or ongoing, stress, as opposed to historical events, weeks or months in the past.

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Time-of-day-dependent adaptation of the HPA axis to predictable social defeat stress

Journal of Endocrinology ◽

10.1530/joe-16-0163 ◽

2016 ◽

Vol 231 (3) ◽

pp. 209-221 ◽

Cited By ~ 7

Author(s):

C E Koch ◽

M S Bartlang ◽

J T Kiehn ◽

L Lucke ◽

N Naujokat ◽

...

Keyword(s):

Hpa Axis ◽

Stress Responses ◽

Molecular Mechanisms ◽

Social Defeat ◽

Time Of Day ◽

Adaptive Responses ◽

Social Defeat Stress ◽

Flight Behaviour ◽

Hpa Axis Activity ◽

The Impact

In modern societies, the risk of developing a whole array of affective and somatic disorders is associated with the prevalence of frequent psychosocial stress. Therefore, a better understanding of adaptive stress responses and their underlying molecular mechanisms is of high clinical interest. In response to an acute stressor, each organism can either show passive freezing or active fight-or-flight behaviour, with activation of sympathetic nervous system and the hypothalamus–pituitary–adrenal (HPA) axis providing the necessary energy for the latter by releasing catecholamines and glucocorticoids (GC). Recent data suggest that stress responses are also regulated by the endogenous circadian clock. In consequence, the timing of stress may critically affect adaptive responses to and/or pathological effects of repetitive stressor exposure. In this article, we characterize the impact of predictable social defeat stress during daytime versus nighttime on bodyweight development and HPA axis activity in mice. While 19 days of social daytime stress led to a transient reduction in bodyweight without altering HPA axis activity at the predicted time of stressor exposure, more detrimental effects were seen in anticipation of nighttime stress. Repeated nighttime stressor exposure led to alterations in food metabolization and reduced HPA axis activity with lower circulating adrenocorticotropic hormone (ACTH) and GC concentrations at the time of predicted stressor exposure. Our data reveal a circadian gating of stress adaptation to predictable social defeat stress at the level of the HPA axis with impact on metabolic homeostasis underpinning the importance of timing for the body’s adaptability to repetitive stress.

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The Influence of HPA-Axis Activity on Aggression

PsycEXTRA Dataset ◽

10.1037/e554382012-121 ◽

2008 ◽

Author(s):

Robina Khan ◽

Katja Bertsch ◽

Ewald Naumann ◽

Menno R. Kruk ◽

Patrick Britz ◽

...

Keyword(s):

Hpa Axis ◽

Hpa Axis Activity

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Geschlechtsunterschiede in Glucocorticoidkonzentrationen und Entzündungsparametern im Zusammenhang mit Depression

Nervenheilkunde ◽

10.1055/a-1033-9899 ◽

2020 ◽

Vol 39 (04) ◽

pp. 222-237

Author(s):

Lena Schneider ◽

Andreas Walther

Keyword(s):

Sex Differences ◽

Major Depression ◽

Hpa Axis ◽

Web Of Science ◽

Tnf Alpha ◽

Mesh Terms

ZusammenfassungHintergrund: Frauen erkranken fast doppelt so häufig wie Männer an einer Major Depression. Eine Hyperaktivität der Hypothalamus-Hypophysen-Nebennierenrinden-Achse (HHNA) und eine chronisch niedrig-gradige Inflammation sind 2 der konsistentesten biologischen Befunde bei schweren Depressionen. Inwiefern diese Parameter für die Existenz von Geschlechtsunterschieden bei Depression eine Rolle spielen, ist noch unzureichend untersucht worden. Methoden: Es wurde eine systematische Literaturrecherche mittels der elektronischen Fachdatenbanken (PubMed, Web of Science, PsycARTICLES) durchgeführt. Die Suche umfasste alle englischsprachigen Artikel, die bis zum 29. Juni 2019 aufgenommen wurden. Als MeSH terms wurden depression, sex differences, inflammation, hpa axis, mit Zusätzen wie cortisol, crp, IL-6, TNF-alpha, dex/crh oder tsst verwendet. Ergebnisse: Insgesamt konnten 62 Primärstudien mit einem Total von 91318 Probanden (52 % Frauen) eingeschlossen werden. Basale Glucocorticoidkonzentrationen scheinen für beide Geschlechter tendenziell positiv mit dem Vorliegen oder der Schwere einer Depressionssymptomatik assoziiert zu sein. Konsistente Geschlechtsunterschiede konnten für die Cortisolreaktion auf einen Stressor sowie für Entzündungsmarker identifiziert werden. Fazit: Geschlechtsunterschiede in der Neurobiologie der Depression sind identifizierbar und geben Anlass für geschlechtsspezifische Untersuchungen der Pathophysiologie von Depressionen und deren geschlechtsspezifischer Behandlungen.

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