title: Increases in mature brain-derived neurotrophic factor protein in the frontal cortex and basal forebrain during chronic sleep restriction in rats: possible role in initiating allostatic adaptation.
abstract: Chronic sleep restriction (CSR) has various negative consequences on cognitive performance and health. Using a rat model of CSR that uses alternating cycles of 3h of sleep deprivation (using slowly rotating activity wheels) and 1h of sleep opportunity continuously for 4 days ('3/1' protocol), we previously observed not only homeostatic but also allostatic (adaptive) sleep responses to CSR. In particular, non-rapid eye movement sleep (NREMS) electroencephalogram (EEG) delta power, an index of sleep intensity, increased initially and then declined gradually during CSR, with no rebound during a 2-day recovery period. To study underlying mechanisms of these allostatic responses, we examined the levels of brain-derived neurotrophic factor (BDNF), which is known to regulate NREMS EEG delta activity, during the same CSR protocol. Mature BDNF protein levels were measured in the frontal cortex and basal forebrain, two brain regions involved in sleep and EEG regulation, and the hippocampus, using Western blot analysis. Adult male Wistar rats were housed in motorized activity wheels, and underwent the 3/1 CSR protocol for 27 h, for 99 h, or for 99 h followed by 24h of recovery. Additional rats were housed in either locked wheels (locked wheel controls [LWCs]) or unlocked wheels that rats could rotate freely (wheel-running controls [WRCs]). BDNF levels did not differ between WRC and LWC groups. BDNF levels were increased, compared to the control levels, in all three brain regions after 27 h, and were increased less strongly after 99 h, of CSR. After 24h of recovery, BDNF levels were at the control levels. This time course of BDNF levels parallels the previously reported changes in NREMS delta power during the same CSR protocol. Changes in BDNF protein levels in the cortex and basal forebrain may be part of the molecular mechanisms underlying allostatic sleep responses to CSR.
authors.affiliation: Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: J K
authors.initials: JK
authors.lastname: Wallingford
authors.affiliation: Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Deurveilher
authors.affiliation: Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: R W
authors.initials: RW
authors.lastname: Currie
authors.affiliation: Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Surgery, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: J P
authors.initials: JP
authors.lastname: Fawcett
authors.affiliation: Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Psychology & Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address: semba@dal.ca.
authors.forename: K
authors.initials: K
authors.lastname: Semba
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000311:Adrenal Glands / Q000502:physiology; D000818:Animals; D066187:Basal Forebrain / Q000378:metabolism*; D015153:Blotting, Western; D001835:Body Weight; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002908:Chronic Disease; D005625:Frontal Lobe / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009929:Organ Size; D011897:Random Allocation; D017208:Rats, Wistar; D012892:Sleep Deprivation / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: Western blot; allostasis; basal forebrain; frontal cortex; hippocampus; sleep deprivation