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Antidepressant effects of sleep deprivation require astrocyte-dependent adenosine mediated signaling.

ABSTRACT: Major depressive disorder is a debilitating condition with a lifetime risk of ten percent. Most treatments take several weeks to achieve clinical efficacy, limiting the ability to bring instant relief needed in psychiatric emergencies. One intervention that rapidly alleviates depressive symptoms is sleep deprivation; however, its mechanism of action is unknown. Astrocytes regulate responses to sleep deprivation, raising the possibility that glial signaling mediates antidepressive-like actions of sleep deprivation. Here, we found that astrocytic signaling to adenosine (A1) receptors was required for the robust reduction of depressive-like behaviors following 12 hours of sleep deprivation. As sleep deprivation activates synaptic A1 receptors, we mimicked the effect of sleep deprivation on depression phenotypes by administration of the A1 agonist CCPA. These results provide the first mechanistic insight into how sleep deprivation impacts mood, and provide a novel pathway for rapid antidepressant development by modulation of glial signaling in the brain.

SUBMITTER: Hines DJ

PROVIDER: S-EPMC3566717 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Antidepressant effects of sleep deprivation require astrocyte-dependent adenosine mediated signaling.

Hines D J DJ Schmitt L I LI Hines R M RM Moss S J SJ Haydon P G PG

Translational psychiatry 20130115

Major depressive disorder is a debilitating condition with a lifetime risk of ten percent. Most treatments take several weeks to achieve clinical efficacy, limiting the ability to bring instant relief needed in psychiatric emergencies. One intervention that rapidly alleviates depressive symptoms is sleep deprivation; however, its mechanism of action is unknown. Astrocytes regulate responses to sleep deprivation, raising the possibility that glial signaling mediates antidepressive-like actions of ...[more]

PMID: 23321809

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Project description:Study objectiveSlow wave activity (SWA) during NREM sleep is the best characterized marker of sleep homeostasis, and the occurrence of sleep slow waves is necessary to reduce sleep need. Recent evidence suggests that sleep slow waves may mediate several beneficial effects of sleep on performance, from the prevention of cognitive impairments to memory consolidation. However, slow waves are also triggered by low doses of many anesthetics, but very few reports have examined whether anesthesia-mediated slow waves affect the homeostatic regulation of sleep. Moreover, no study has examined how sleep is affected by higher doses of anesthetics, which lead to a predominantly "isoelectric" EEG tracing without slow waves.DesignWe studied in rats whether 1 hour of a dose of isoflurane or desflurane able to induce almost continuous slow waves (ISO-sw, DES-sw), and of a dose of desflurane resulting in a predominantly isoelectric EEG (DES-iso) reduces the sleep pressure caused by 4 h of sleep deprivation. Anesthesia was compared to a mock condition in which rats were only anesthetized for 2-3 min.SettingBasic sleep research laboratory.Patients or participantsMale WKY rats (n=31).InterventionsTotal sleep deprivation by exposure to novel objects starting at light onset, followed by one hour of anesthesia or mock anesthesia.Measurements and resultsOne hour of anesthesia (sw or iso) did not affect either sleep duration or the overall sleep pattern. Anesthesia with ISO-sw or DES-sw, both associated with the occurrence of almost continuous slow waves, reduced the SWA rebound expected following 4 h of sleep deprivation. One hour of anesthesia with DES-iso, associated with isoelectric EEG and few slow waves, also reduced the SWA rebound after sleep deprivation, and did so to an extent similar to that observed after DES-sw. However, in contrast to DES-sw, SWA after DES-iso remained chronically lower than in baseline, resulting in reduced slow wave energy (SWE, SWA × time) for at least 2 days.ConclusionThe blunted SWA rebound after ISO-sw and DES-sw suggests that anesthesia slow waves may substitute for sleep slow waves. The reduced SWA rebound after DES-iso may reflect a pathological condition that results in a chronic decrease in SWA, or may suggest that anesthesia slow waves are not an absolute requirement to discharge sleep pressure.

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Antidepressant effects of sleep deprivation require astrocyte-dependent adenosine mediated signaling.

Publications

Antidepressant effects of sleep deprivation require astrocyte-dependent adenosine mediated signaling.

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