title: Chromosome 1 replacement increases brain orexins and antidepressive measures without increasing locomotor activity.
abstract: Decreased orexin level has been well demonstrated in patients suffering from narcolepsy, depression accompanied with suicide attempt; obstructive sleep apnea and comorbidity were also demonstrated in these diseases. As C57BL/6J (B6) mice are more "depressed" and have lower brain orexins than A/J mice, B6 mice having chromosome 1 replacement (B6A1 mice) might have restored orexin levels and less depressive behavior. We studied the behavior of 4-6 month old B6, A/J and B6A1 mice with forced swim, tail suspension, and locomotor activity tests. The animals were then sacrificed and hypothalamus and medullas dissected from brain tissue. Orexins-A and -B were determined by radioimmunoassay. Compared with A/J mice, B6 mice displayed several signs of depression, including increased immobility, increased locomotors activity, and decreased orexin A and -B levels in both the hypothalamus and medulla. Compared to B6 mice, B6A1 mice exhibited significantly higher levels of orexins-A and -B in both brain regions. B6A1 mice also exhibited antidepressive features in most of measured variables, including decreased locomotor activity, decreased immobility and increased swim in tail suspension test; compared with B6 mice, however. B6A1 mice also reversed immobility in the early phase of the swim test. In summary, B6 mice exhibited depressive attributes compared with A/J mice, including increased locomotor activity, greater immobility, and decreased brain orexins, these were largely reversed in B6A1 mice. We conclude that orexin levels modulate these B6 behaviors, likely due to expression of A/J alleles on Chromosome 1.
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA; Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA. Electronic address: dxpfeng@gmail.com.
authors.forename: Pingfu
authors.initials: P
authors.lastname: Feng
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA; Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA.
authors.forename: Yufen
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Drina
authors.initials: D
authors.lastname: Vurbic
authors.affiliation: Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA.
authors.forename: Afaf
authors.initials: A
authors.lastname: Akladious
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA; Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA.
authors.forename: Kingman P
authors.initials: KP
authors.lastname: Strohl
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003866:Depressive Disorder / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D019417:Hindlimb Suspension; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000235:genetics; D009479:Neuropeptides / Q000378:metabolism*; D000068797:Orexins; D011863:Radioimmunoassay; D013550:Swimming / Q000523:psychology
chemical_list: C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins
keywords: Chromosome substitution; Depression; Immobility; Orexin