title: Chronic sleep restriction elevates brain interleukin-1 beta and tumor necrosis factor-alpha and attenuates brain-derived neurotrophic factor expression.
abstract: Acute sleep loss increases pro-inflammatory and synaptic plasticity-related molecules in the brain, including interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and brain-derived neurotrophic factor (BDNF). These molecules enhance non-rapid eye movement sleep slow wave activity (SWA), also known as electroencephalogram delta power, and modulate neurocognitive performance. Evidence suggests that chronic sleep restriction (CSR), a condition prevalent in today's society, does not elicit the enhanced SWA that is seen after acute sleep loss, although it cumulatively impairs neurocognitive functioning. Rats were continuously sleep deprived for 18h per day and allowed 6h of ad libitum sleep opportunity for 1 (SR1), 3 (SR3), or 5 (SR5) successive days (i.e., CSR). IL-1β, TNF-α, and BDNF mRNA levels were determined in the somatosensory cortex, frontal cortex, hippocampus, and basal forebrain. Largely, brain IL-1β and TNF-α expression were significantly enhanced throughout CSR. In contrast, BDNF mRNA levels were similar to baseline values in the cortex after 1 day of SR and significantly lower than baseline values in the hippocampus after 5 days of SR. In the basal forebrain, BDNF expression remained elevated throughout the 5 days of CSR, although IL-1β expression was significantly reduced. The chronic elevations of IL-1β and TNF-α and inhibition of BDNF might contribute to the reported lack of SWA responses reported after CSR. Further, the CSR-induced enhancements in brain inflammatory molecules and attenuations in hippocampal BDNF might contribute to neurocognitive and vigilance detriments that occur from CSR.
authors.affiliation: Department of Psychiatry, Harvard Medical School and Veterans Affairs Boston Healthcare System, West Roxbury, MA 02132, USA. Electronic address: Mark_Zielinski@hms.harvard.edu.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Zielinski
authors.affiliation: Department of Psychiatry, Harvard Medical School and Veterans Affairs Boston Healthcare System, Brockton, MA 02301, USA.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Psychiatry, Harvard Medical School and Veterans Affairs Boston Healthcare System, West Roxbury, MA 02132, USA.
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Karpova
authors.affiliation: Department of Psychiatry, Harvard Medical School and Veterans Affairs Boston Healthcare System, Brockton, MA 02301, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: McCarley
authors.affiliation: Department of Psychiatry, Harvard Medical School and Veterans Affairs Boston Healthcare System, Brockton, MA 02301, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Strecker
authors.affiliation: Department of Psychiatry, Harvard Medical School and Veterans Affairs Boston Healthcare System, West Roxbury, MA 02132, USA.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Gerashchenko
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012892:Sleep Deprivation / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D053583:Interleukin-1beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha
keywords: Brain-derived neurotropic factor; Cytokine; Interleukin-1 beta; Sleep deprivation; Sleep restriction; Tumor necrosis factor-alpha
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