title: Hypobaric hypoxia modulates brain biogenic amines and disturbs sleep architecture.
abstract: Sojourners to high altitude experience poor-quality of sleep due to hypobaric hypoxia (HH). Brain neurotransmitters are the key regulators of sleep wakefulness. Scientific literature has limited information on the role of brain neurotransmitters involved in sleep disturbance in HH. The present study aimed to investigate the time dependent changes in neurotransmitter levels and enzymes involved in the biosynthesis of brain neurotransmitters in frontal cortex, brain stem, cerebellum, pons and medulla and the effect of these alterations on sleep architecture in HH. Thirty adult Sprague-Dawley rats, body weight of 230-250 g were exposed to simulated altitude ∼7620 m, 282 mm Hg, partial pressure of O(2) 59 mm Hg for 7 and 14 days continuously in an animal decompression chamber. After 7 and 14 days of HH, brain nor-epinephrine and dopamine levels were significantly increased in frontal cortex, brain stem, cerebellum and pons and medulla whereas serotonin level was significantly reduced in frontal cortex and pons and medulla after 14 days of HH. Tyrosine hydroxylase level in locus coeruleus (LC) was significantly increased whereas Choline Acetyl Transferase and Glutamic Acid Decarboxylase (GAD) levels were significantly reduced in laterodorsal-tegmentum and pedunculopontine-tegmentum after 7 days of HH. GAD was also reduced in LC after 7 days HH. Alteration in these neurotransmitters and enzyme levels was accompanied with reduction in quality and quantity of sleep. There was a significant increase in sleep latency, rapid eye movement (REM) latency, duration of active awake, quiet awake, quiet sleep and a significant decrease in duration of REM sleep and deep sleep on day 7 and 14 of HH. It was concluded that HH alters the expression of enzymes linked to sleep neurotransmitter synthesis pathway and subsequent loss of homeostasis at neurotransmitter level disrupts the sleep pattern in hypobaric hypoxia.
authors.affiliation: Neurophysiology Division, Department of Physiology, Defence Institute of Physiology & Allied Sciences, Defence Research and Development Organization, Timarpur, Delhi, India.
authors.forename: Koushik
authors.initials: K
authors.lastname: Ray
authors.forename: Arkadeb
authors.initials: A
authors.lastname: Dutta
authors.forename: Usha
authors.initials: U
authors.lastname: Panjwani
authors.forename: Lalan
authors.initials: L
authors.lastname: Thakur
authors.forename: J P
authors.initials: JP
authors.lastname: Anand
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
mesh_terms: D000399:Air Pressure; D000531:Altitude; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001923:Brain Chemistry / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D004567:Electrodes, Implanted; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D017286:Polysomnography; D011301:Preoptic Area / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D012894:Sleep Stages / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D001679:Biogenic Amines; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D004298:Dopamine; D009638:Norepinephrine