Department of Psychology, Simon Fraser University, Burnaby, BC, Canada V5A 1S6.
Neuroscience. 2011 Oct 13;193:170-81. doi: 10.1016/j.neuroscience.2011.07.019. Epub 2011 Jul 14.
Procedures that restrict or fragment sleep can inhibit neurogenesis in the hippocampus of adult rodents, although the underlying mechanism is unknown. We showed that rapid-eye-movement (REM) sleep deprivation (RSD) by the platform-over-water method inhibits hippocampal cell proliferation in adrenalectomized rats with low-dose corticosterone clamp. This procedure also greatly disrupts daily behavioral rhythms. Given recent evidence for circadian clock regulation of cell proliferation, we asked whether disruption of circadian rhythms might play a role in the anti-neurogenic effects of sleep loss. Male Sprague-Dawley rats were subjected to a 4-day RSD procedure or were exposed to constant bright light (LL) for 4 days or 10 weeks, a non-invasive procedure for eliminating circadian rhythms of behavior and physiology in this species. Proliferating cells in the granule cell layer of the dentate gyrus were identified by immunolabeling for the thymidine analogue 5-bromo-2-deoxyuridine. Consistent with our previous results, the RSD procedure suppressed cell proliferation by ∼50%. By contrast, although LL attenuated or eliminated daily rhythms of activity and sleep-wake without affecting daily amounts of REM sleep, cell proliferation was not affected. Melatonin, a nocturnally secreted neurohormone that is inhibited by light, has been shown to promote survival of new neurons. We found that 3-weeks of LL eliminated daily rhythms and decreased plasma melatonin by 88% but did not significantly affect either total cell survival or survival of new neurons (doublecortin+). Finally, we measured cell proliferation rates at the beginning and near the end of the daily light period in rats entrained to a 12:12 light/lark (LD) cycle, but did not detect a daily rhythm. These results indicate that the antineurogenic effect of RSD is not secondary to disruption of circadian rhythms, and provide no evidence that hippocampal cell proliferation and survival are regulated by the circadian system or by nocturnal secretion of pineal melatonin.
限制或分割睡眠的程序会抑制成年啮齿动物海马体中的神经发生，尽管其潜在机制尚不清楚。我们表明，通过平台水法进行快速眼动 (REM) 睡眠剥夺 (RSD) 会抑制低剂量皮质酮钳夹的肾上腺切除大鼠中海马细胞增殖。该程序还极大地破坏了日常行为节律。鉴于最近有证据表明生物钟调节细胞增殖，我们想知道昼夜节律的破坏是否在睡眠不足的抗神经发生作用中起作用。雄性 Sprague-Dawley 大鼠接受了为期 4 天的 RSD 程序或暴露于持续明亮的光（LL）4 天或 10 周，这是一种消除该物种行为和生理昼夜节律的非侵入性程序。通过免疫标记胸腺嘧啶类似物 5-溴-2-脱氧尿苷来鉴定齿状回颗粒细胞层中的增殖细胞。与我们之前的结果一致，RSD 程序抑制了约 50%的细胞增殖。相比之下，尽管 LL 减弱或消除了活动和睡眠-觉醒的日常节律，而不影响 REM 睡眠的日常量，但细胞增殖不受影响。褪黑素是一种在夜间分泌的神经激素，会被光抑制，已被证明可以促进新神经元的存活。我们发现，3 周的 LL 消除了日常节律并使血浆褪黑素减少了 88%，但对总细胞存活或新神经元（双皮质素+）的存活没有显著影响。最后，我们在适应 12:12 光照/黎明（LD）周期的大鼠中测量了开始和接近每日光照期结束时的细胞增殖率，但未检测到日常节律。这些结果表明，RSD 的抗神经发生作用不是由于昼夜节律的破坏引起的，并且没有证据表明海马体细胞增殖和存活受昼夜节律系统或松果体褪黑素的夜间分泌调节。
