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Arnsten AFT. Stress signaling pathways that impair prefrontal cortex structure and function. Nat Res Neurosci 10: 410-422

Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Nature Reviews Neuroscience (Impact Factor: 31.43). 07/2009; 10(6):410-22. DOI: 10.1038/nrn2648
Source: PubMed

ABSTRACT

The prefrontal cortex (PFC) - the most evolved brain region - subserves our highest-order cognitive abilities. However, it is also the brain region that is most sensitive to the detrimental effects of stress exposure. Even quite mild acute uncontrollable stress can cause a rapid and dramatic loss of prefrontal cognitive abilities, and more prolonged stress exposure causes architectural changes in prefrontal dendrites. Recent research has begun to reveal the intracellular signalling pathways that mediate the effects of stress on the PFC. This research has provided clues as to why genetic or environmental insults that disinhibit stress signalling pathways can lead to symptoms of profound prefrontal cortical dysfunction in mental illness.

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    • "Thereafter, hyperactivity of HPA axis elevates the level of corticosterone which further affects the cognitive function (Harvey et al., 2006). On the other hand, SAM system increases the catecholamines level to strengthen the fear conditioning during stress (Arnsten, 2009). Studies have proved that chronic restraint stress in the rodents results in neurobehavioural abnormalities such as anxiety, depressive illness as well as cognitive impairment (Ferraz et al., 2011; Kim and Han, 2006; Tian et al., 2013; Vyas and Chattarji, 2004). "
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    • "On the one hand, neuroticism and related traits (e.g., anxiety) seem to generally diminish processing efficiency through disadvantageous arousal level as well as emotional and cognitive resource-demanding interferences , such as worrisome thoughts or negative emotions. On the other hand, in accordance with many studies showing the effect of distress on aggravated operations in the prefrontal cortex (for a review, see Arnsten, 2009), neuroticism-related characteristics seem to mainly reduce resources available to control attention by impairing processes in the central executive of WM (e.g., Bishop, 2009; Derakshan & Eysenck, 2009; Eysenck & Calvo, 1992; Eysenck, Derakshan, Santos, & Calvo, 2007; Gray et al., 2005; Schmeichel, Volokhov, & Demaree, 2008; Shackman et al., 2006). These assumptions were confirmed in neuroimaging studies revealing that neuroticism is associated with reduced neuronal efficiency and impoverished recruitment of prefrontal attention control mechanisms during a WM task (Bishop, 2009; Gray et al., 2005). "
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    • "• Researchers could develop treatments that target withdrawal symptoms and stress-related pathology, such as stress-induced craving and alcohol seeking, implicated by the alcohol-related neuroadaptations in the PSL circuit. For instance, alpha1-adrenergic antagonists, such as Prazosin, show promise for improving stress-induced deficits and impaired PFC function from chronic stress (for a review, see Arnsten 2009). This drug also reduces alcohol withdrawal symptoms and stress-related alcohol seeking in animals (Kukolja et al. 2011; Walker et al. 2008) and improves stress and alcohol cue– induced craving and alcohol use outcomes in humans (Fox et al. 2012; Simpson et al. 2009). "
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