Circadian genes <i><scp>P</scp>eriod 1</i> and <i><scp>P</scp>eriod 2</i> in the nucleus accumbens regulate anxiety‐related behavior

Spencer, Sade; Falcón, Edgardo; Kumar, Jaswinder; Krishnan, Vaishnav; Mukherjee, Shibani; Birnbaum, Shari G.; McClung, Colleen A.

doi:10.1111/ejn.12010

Cited by 101 publications

(86 citation statements)

References 61 publications

(85 reference statements)

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“…Similar to peripheral tissues, GR may bind to glucocorticoid response promoter elements to enhance the expression of Per1 and Per2 (38–40). Previously, we implicated the Per genes in response to stress and anxiety behavior specifically in the NAc (41). It is possible that chronic stress enhances the amplitude of local molecular clocks in the NAc independently of SCN-derived inputs, possibly through GC signaling.…”

Section: Discussionmentioning

confidence: 99%

Chronic Stress Induces Brain Region-Specific Alterations of Molecular Rhythms that Correlate with Depression-like Behavior in Mice

Logan

Edgar

Gillman

et al. 2015

Biological Psychiatry

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Background Emerging evidence implicates circadian abnormalities as a component of the pathophysiology of major depressive disorder (MDD). The suprachiasmatic nucleus (SCN) of the hypothalamus coordinates rhythms throughout the brain and body. On a cellular level, rhythms are generated by transcriptional, translational, and post-translational feedback loops of core circadian genes and proteins. In patients with MDD, recent evidence suggests reduced amplitude of molecular rhythms in extra-SCN brain regions. We investigated whether unpredictable chronic mild stress (UCMS), an animal model that induces a depression-like physiological and behavioral phenotype, induces circadian disruptions similar to those seen with MDD. Methods Activity and temperature rhythms were recorded in C57BL/6J mice before, during, and after exposure to UCMS, and brain tissue explants were collected from Period2 luciferase (Per2::luc) mice following UCMS to assess cellular rhythmicity. Results UCMS significantly decreased circadian amplitude of activity and body temperature in mice, similar to findings in MDD patients and these changes directly correlate with depression-related behavior. While amplitude of molecular rhythms in the SCN was decreased following UCMS, surprisingly, rhythms in the nucleus accumbens were amplified with no changes seen in the prefrontal cortex or amygdala. These molecular rhythm changes in the SCN and the nucleus accumbens (NAc) also directly correlated with mood-related behavior. Conclusions These studies find that circadian rhythm abnormalities directly correlate with depression-related behavior following UCMS and suggest a desynchronization of rhythms in the brain with an independent enhancement of rhythms in the NAc.

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Section: Discussionmentioning

confidence: 99%

Chronic Stress Induces Brain Region-Specific Alterations of Molecular Rhythms that Correlate with Depression-like Behavior in Mice

Logan

Edgar

Gillman

et al. 2015

Biological Psychiatry

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123

100

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“…[102]. The Dbp -/-mouse is hypoactive at baseline, but hyperactive when exposed to chronic stress, modeling to some extent the alternating depression-like and mania-like behavior seen in BD.…”

Section: Major Depressive Disorder (Mdd) and Bipolar Disorder (Bd)mentioning

confidence: 98%

Circadian Clock and Stress Interactions in the Molecular Biology of Psychiatric Disorders

Landgraf

McCarthy

Welsh

2014

Curr Psychiatry Rep

140

100

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Many psychiatric disorders are characterized by circadian rhythm abnormalities including disturbed sleep/wake cycles, changes in locomotor activity, and abnormal endocrine function. Animal models with mutations in circadian "clock genes" commonly show disturbances in reward processing, locomotor activity and novelty seeking behaviors, further supporting the idea of a connection between the circadian clock and psychiatric disorders. However, if circadian clock dysfunction is a common risk factor for multiple psychiatric disorders, it is unknown if and how these putative clock abnormalities could be expressed differently, and contribute to multiple, distinct phenotypes. One possible explanation is that the circadian clock modulates the biological responses to stressful environmental factors that vary with an individual's experience. It is known that the circadian clock and the stress response systems are closely related: Circadian clock genes regulate the physiological sensitivity to, and rhythmic release of glucocorticoids (GC). In turn, GCs have reciprocal effects on the clock. Since stressful life events or increased vulnerability to stress are risk factors for multiple psychiatric disorders including posttraumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), major depressive disorder (MDD), alcohol use disorder (AUD) and schizophrenia (SCZ), we propose that modulation of the stress response is a common mechanism by which circadian clock genes affect these illnesses. Presently, we review how molecular components of the circadian clock may contribute to these six psychiatric disorders, and present the hypothesis that modulation of the stress response may constitute a common mechanism by which the circadian clock affects multiple psychiatric disorders.

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“…Per2 mutant mice do not have consistent behavioral abnormalities in tests that induce anxietylike behaviors, but mice deficient in both Per1 and Per2 have increases in the level of anxiety-like behaviors in more than one measure (Spencer et al, 2013). Finally, and a bit paradoxically, Per2 mutant mice have increases in alcohol intake (Gamsby et al, 2013;Spanagel, Pendyala, et al, 2005).…”

Section: Anxiety Disordersmentioning

confidence: 99%

Clock genes in human alcohol abuse and comorbid conditions

Partonen

2015

Alcohol

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Circadian genes Period 1 and Period 2 in the nucleus accumbens regulate anxiety‐related behavior

Cited by 101 publications

References 61 publications

Chronic Stress Induces Brain Region-Specific Alterations of Molecular Rhythms that Correlate with Depression-like Behavior in Mice

Chronic Stress Induces Brain Region-Specific Alterations of Molecular Rhythms that Correlate with Depression-like Behavior in Mice

Circadian Clock and Stress Interactions in the Molecular Biology of Psychiatric Disorders

Clock genes in human alcohol abuse and comorbid conditions

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