Feng Pingfu, Hu Yufen, Vurbic Drina, Akladious Afaf, Strohl Kingman P
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.
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.
J Psychiatr Res. 2014 Dec;59:140-7. doi: 10.1016/j.jpsychires.2014.08.008. Epub 2014 Aug 23.
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.
在发作性睡病、伴有自杀企图的抑郁症患者中，食欲素水平降低已得到充分证实；阻塞性睡眠呼吸暂停及其合并症在这些疾病中也有体现。由于C57BL/6J（B6）小鼠比A/J小鼠更“抑郁”且脑内食欲素水平更低，具有1号染色体替换的B6小鼠（B6A1小鼠）可能恢复了食欲素水平且抑郁行为减少。我们通过强迫游泳、悬尾和自发活动测试研究了4 - 6月龄B6、A/J和B6A1小鼠的行为。然后处死动物，从脑组织中分离出下丘脑和延髓。通过放射免疫分析法测定食欲素A和食欲素B。与A/J小鼠相比，B6小鼠表现出多种抑郁迹象，包括不动时间增加、自发活动增加，以及下丘脑和延髓中食欲素A和食欲素B水平降低。与B6小鼠相比，B6A1小鼠在两个脑区的食欲素A和食欲素B水平均显著更高。B6A1小鼠在大多数测量变量中也表现出抗抑郁特征，包括自发活动减少、不动时间减少以及悬尾测试中游泳时间增加；然而，与B6小鼠相比，B6A1小鼠在游泳测试早期也逆转了不动状态。总之，与A/J小鼠相比，B6小鼠表现出抑郁特征，包括自发活动增加、不动时间延长以及脑内食欲素减少，而这些在B6A1小鼠中大多得到逆转。我们得出结论，食欲素水平调节这些B6小鼠的行为，可能是由于1号染色体上A/J等位基因的表达。
