Prefrontal Cortex Corticotropin-Releasing Factor Receptor 1 Conveys Acute Stress-Induced Executive Dysfunction

Uribe-Mariño, A.; Gassen, Nils C.; Wiesbeck, Maximilian F.; Balsevich, Georgia; Santarelli, Sara; Solfrank, Beate; Dournes, Carine; Fries, Gabriel R.; Masana, Mercè; Labermeier, Christiana; Wang, Xiaodong; Hafner, Kathrin; Schmid, Bianca; Rein, Theo; Chen, Alon; Deussing, Jan M.; Schmidt, Mathias

doi:10.1016/j.biopsych.2016.03.2106

Cited by 79 publications

(75 citation statements)

References 54 publications

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“…For example, stress upregulates sex hormones (Lennartsson et al, 2012a), alters immune system activity (Segerstrom and Miller, 2004; Steptoe et al, 2007), and upregulates other adrenal hormones such as DHEA or noradrenaline (Allen et al, 2014; Lennartsson et al, 2012b; Shields et al, 2016a; Thoma et al, 2012), and many of these hormones and immune system factors exert effects on cognition (Allen et al, 2014; Mehta and Josephs, 2010; Shields et al, 2016a; Sparkman et al, 2006). Similarly, stress alters catecholaminergic activity and corticotropin-releasing hormone (CRH), both of which have known and important effects on executive function (Arnsten, 2009; Shansky and Lipps, 2013; Uribe-Mariño et al, 2016). As such, effects of stress on any one of these biological processes may be responsible in part for stress effects on executive functions, and a failure to consider them may result in an incomplete picture of how stress influences executive functions.…”

Section: Discussionmentioning

confidence: 99%

The effects of acute stress on core executive functions: A meta-analysis and comparison with cortisol

Shields

Sazma

Yonelinas

2016

Neuroscience & Biobehavioral Reviews

541

473

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Core executive functions such as working memory, inhibition, and cognitive flexibility are integral to daily life. A growing body of research has suggested that acute stress may impair core executive functions. However, there are a number of inconsistencies in the literature, leading to uncertainty about how or even if acute stress influences core executive functions. We addressed this by conducting a meta-analysis of acute stress effects on working memory, inhibition, and cognitive flexibility. We found that stress impaired working memory and cognitive flexibility, whereas it had nuanced effects on inhibition. Many of these effects were moderated by other variables, such as sex. In addition, we compared effects of acute stress on core executive functions to effects of cortisol administration and found some striking differences. Our findings indicate that stress works through mechanisms aside from or in addition to cortisol to produce a state characterized by more reactive processing of salient stimuli but greater control over actions. We conclude by highlighting some important future directions for stress and executive function research.

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Section: Discussionmentioning

confidence: 99%

The effects of acute stress on core executive functions: A meta-analysis and comparison with cortisol

Shields

Sazma

Yonelinas

2016

Neuroscience & Biobehavioral Reviews

541

473

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“…Using Western blotting, this antibody recognizes a 43 kDa band selective for pCREB (manufacturer information). This antibody has been utilized to detect neural activation within CRFR1‐GFP labeled cells using the CRFR1‐BAC mouse line (Uribe‐Mariño et al, ). Our studies also indicate that little pCREB is present in the hypothalamus of resting mice while it is abundant following psychogenic stress (Figure c,d).…”

Section: Methodsmentioning

confidence: 99%

Characterization and gonadal hormone regulation of a sexually dimorphic corticotropin‐releasing factor receptor 1 cell group

Rosinger

Jacobskind

Bulanchuk

et al. 2018

J of Comparative Neurology

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Corticotropin‐releasing factor binds with high affinity to CRF receptor 1 (CRFR1) and is implicated in stress‐related mood disorders such as anxiety and depression. Using a validated CRFR1‐green fluorescent protein (GFP) reporter mouse, our laboratory recently discovered a nucleus of CRFR1 expressing cells that is prominent in the female rostral anteroventral periventricular nucleus (AVPV/PeN), but largely absent in males. This sex difference is present in the early postnatal period and remains dimorphic into adulthood. The present investigation sought to characterize the chemical composition and gonadal hormone regulation of these sexually dimorphic CRFR1 cells using immunohistochemical procedures. We report that CRFR1‐GFP‐ir cells within the female AVPV/PeN are largely distinct from other dimorphic cell populations (kisspeptin, tyrosine hydroxylase). However, CRFR1‐GFP‐ir cells within the AVPV/PeN highly co‐express estrogen receptor alpha as well as glucocorticoid receptor. A single injection of testosterone propionate or estradiol benzoate on the day of birth completely eliminates the AVPV/PeN sex difference, whereas adult gonadectomy has no effect on CRFR1‐GFP cell number. These results indicate that the AVPV/PeN CRFR1 is regulated by perinatal but not adult gonadal hormones. Finally, female AVPV/PeN CRFR1‐GFP‐ir cells are activated following an acute 30‐min restraint stress, as assessed by co‐localization of CRFR1‐GFP cells with phosphorylated (p) CREB. CRFR1‐GFP/pCREB cells were largely absent in the male AVPV/PeN. Together, these data indicate a stress and gonadal hormone responsive nucleus that is unique to females and may contribute to sex‐specific stress responses.

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“…Prefrontal CRHR1s have been associated with anxiety (Sotnikov et al, 2014), contribute to the HPA-axis stress response (Jaferi and Bhatnagar, 2007) and were recently found to mediate acute stress-induced executive dysfunction (Uribe-Marino et al, 2016). MS has been observed to significantly increase CRHR1 protein levels in response to acute stress, compared to non-MS controls (O'Malley et al, 2011).…”

Section: Hpa-axis Programming By Early Life Stress (Els)mentioning

confidence: 99%

Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure

Bodegom

Homberg

Henckens

2017

Front. Cell. Neurosci.

425

331

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Exposure to stress during critical periods in development can have severe long-term consequences, increasing overall risk on psychopathology. One of the key stress response systems mediating these long-term effects of stress is the hypothalamic-pituitary-adrenal (HPA) axis; a cascade of central and peripheral events resulting in the release of corticosteroids from the adrenal glands. Activation of the HPA-axis affects brain functioning to ensure a proper behavioral response to the stressor, but stress-induced (mal)adaptation of the HPA-axis' functional maturation may provide a mechanistic basis for the altered stress susceptibility later in life. Development of the HPA-axis and the brain regions involved in its regulation starts prenatally and continues after birth, and is protected by several mechanisms preventing corticosteroid over-exposure to the maturing brain. Nevertheless, early life stress (ELS) exposure has been reported to have numerous consequences on HPA-axis function in adulthood, affecting both its basal and stress-induced activity. According to the match/mismatch theory, encountering ELS prepares an organism for similar (“matching”) adversities during adulthood, while a mismatching environment results in an increased susceptibility to psychopathology, indicating that ELS can exert either beneficial or disadvantageous effects depending on the environmental context. Here, we review studies investigating the mechanistic underpinnings of the ELS-induced alterations in the structural and functional development of the HPA-axis and its key external regulators (amygdala, hippocampus, and prefrontal cortex). The effects of ELS appear highly dependent on the developmental time window affected, the sex of the offspring, and the developmental stage at which effects are assessed. Albeit by distinct mechanisms, ELS induced by prenatal stressors, maternal separation, or the limited nesting model inducing fragmented maternal care, typically results in HPA-axis hyper-reactivity in adulthood, as also found in major depression. This hyper-activity is related to increased corticotrophin-releasing hormone signaling and impaired glucocorticoid receptor-mediated negative feedback. In contrast, initial evidence for HPA-axis hypo-reactivity is observed for early social deprivation, potentially reflecting the abnormal HPA-axis function as observed in post-traumatic stress disorder, and future studies should investigate its neural/neuroendocrine foundation in further detail. Interestingly, experiencing additional (chronic) stress in adulthood seems to normalize these alterations in HPA-axis function, supporting the match/mismatch theory.

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Prefrontal Cortex Corticotropin-Releasing Factor Receptor 1 Conveys Acute Stress-Induced Executive Dysfunction

Cited by 79 publications

References 54 publications

The effects of acute stress on core executive functions: A meta-analysis and comparison with cortisol

The effects of acute stress on core executive functions: A meta-analysis and comparison with cortisol

Characterization and gonadal hormone regulation of a sexually dimorphic corticotropin‐releasing factor receptor 1 cell group

Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure

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