Feng Pingfu, Akladious Afaf A, Hu Yufen, Raslan Yousef, Feng James, Smith Phillip J
Louis Stokes Cleveland DVA Medical Center, USA; Division of Pulmonary, Critical Care and Sleep Medicine, Case Western Reserve University, Cleveland, OH, USA.
Louis Stokes Cleveland DVA Medical Center, USA.
J Psychiatr Res. 2015 Oct;69:110-9. doi: 10.1016/j.jpsychires.2015.08.002. Epub 2015 Aug 4.
Brain-derived neurotrophic factor (BDNF) binds to Tropomyosin-receptor-kinase B (TrkB) receptors that regulate synaptic strength and plasticity in the mammalian nervous system. 7,8-Dihydroxyflavone (DHF) is a recently identified small molecule Trk B agonist that has been reported to ameliorate depression, attenuate the fear response, improve memory consolidation, and exert neuroprotective effects. Poor and disturbed sleep remains a symptom of major depressive disorder and most current antidepressants affect sleep. Therefore, we conducted sleep/wake recordings and concomitant measurement of brain orexins, endogenous peptides that suppress sleep, in mice for this study. Baseline polysomnograph recording was performed for 24 h followed by treatment with either 5 mg/kg of DHF or vehicle at the beginning of the dark phase. Animals were sacrificed the following day, one hour after the final treatment with DHF. Orexin A and B were quantified using ELISA and radioimmunoassay, respectively. Total sleep was significantly decreased in the DHF group, 4 h after drug administration in the dark phase, when compared with vehicle-treated animals. This difference was due to a significant decrease of non-rapid eye movement sleep, but not rapid eye movement sleep. DHF increased power of alpha and sigma bands but suppressed power of gamma band during sleep in dark phase. Interestingly, hypothalamic levels of orexin A were also significantly decreased in the DHF group (97 pg/mg) when compared with the vehicle-treated group (132 pg/mg). However, no significant differences of orexin B were observed between groups. Additionally, no change was found in immobility tests.
脑源性神经营养因子（BDNF）与原肌球蛋白受体激酶B（TrkB）受体结合，后者调节哺乳动物神经系统中的突触强度和可塑性。7,8-二羟基黄酮（DHF）是最近鉴定出的一种小分子Trk B激动剂，据报道它可改善抑郁、减轻恐惧反应、改善记忆巩固并发挥神经保护作用。睡眠质量差和睡眠紊乱仍是重度抑郁症的症状，并且大多数现有的抗抑郁药都会影响睡眠。因此，在本研究中，我们对小鼠进行了睡眠/清醒记录，并同时测量了大脑中orexins（一种抑制睡眠的内源性肽）。进行24小时的基线多导睡眠图记录，然后在黑暗期开始时用5mg/kg的DHF或赋形剂进行治疗。在最后一次用DHF治疗后一小时，于次日处死动物。分别使用酶联免疫吸附测定（ELISA）和放射免疫测定法定量orexin A和orexin B。与赋形剂处理的动物相比，在黑暗期给药4小时后，DHF组的总睡眠时间显著减少。这种差异是由于非快速眼动睡眠显著减少，而非快速眼动睡眠未减少。在黑暗期睡眠期间，DHF增加了α和σ频段的功率，但抑制了γ频段的功率。有趣的是，与赋形剂处理组（132 pg/mg）相比，DHF组的下丘脑orexin A水平也显著降低（97 pg/mg）。然而，两组之间orexin B未观察到显著差异。此外，在不动测试中未发现变化。
