Neurophysiology Division, Defense Institute of Physiology and Allied Sciences (DIPAS), Defense Research and Development Organization (DRDO), Lucknow Road, Timarpur, Delhi-54, India.
Exp Neurol. 2013 Oct;248:470-81. doi: 10.1016/j.expneurol.2013.07.021. Epub 2013 Aug 3.
It has been established that sleep deprivation (SD) reduces the proliferation of neuronal precursors in the adult hippocampus. It has also been reported that psychostimulant drugs modulate adult neurogenesis. We examined the modulatory role of two psychostimulant drugs modafinil and caffeine on adult neuronal cell proliferation (NCP) during 48 h of total SD. A novel automated cage shaking stimulus was used to induce SD based on animal activity. 5-Bromo-2″-deoxyuridine (BrdU; 50mg/kg/day i.p.) was injected at the onset of the light phase for two days. Rats were successfully sleep deprived for 85-94% of total time. Stereological analysis showed that both caffeine and modafinil treatments during SD improved the number of BrdU positive cells as compared to the SD group. Caffeine treatment during SD, significantly increased early proliferative and post-mitotic stages of doublecortin (DCX) positive cells while modafinil treatment during SD, increased intermediate and post-mitotic stages of DCX positive cells compared to SD+Vehicle group. Brain-Derived Neurotrophic Factor (BDNF) expression on BrdU positive cells as well as in the dentate gyrus (DG) region was decreased significantly after sleep deprivation. Both caffeine and modafinil significantly improved BDNF expression in the DG region. Modafinil, but not caffeine, significantly decreased hippocampal adenosine level during SD in comparison to the SD+Vehicle group. It may be concluded that caffeine or modafinil treatment during 48 h of SD prevents the SD induced decline in neuronal proliferation and differentiation. Caffeine and modafinil induced alterations of NCP during SD may involve modulation of BDNF and adenosine levels.
已经证实，睡眠剥夺（SD）会减少成年海马体神经元前体细胞的增殖。也有报道称，精神兴奋剂会调节成年神经发生。我们研究了两种精神兴奋剂莫达非尼和咖啡因在 48 小时完全 SD 期间对成年神经元细胞增殖（NCP）的调节作用。一种新的自动化笼振动刺激被用于根据动物活动诱导 SD。5-溴-2′-脱氧尿苷（BrdU；50mg/kg/天，腹腔注射）在光照阶段开始时注射两天。大鼠成功地被剥夺了 85-94%的总睡眠时间。立体学分析显示，与 SD 组相比，SD 期间给予咖啡因和莫达非尼治疗均可增加 BrdU 阳性细胞的数量。SD 期间给予咖啡因治疗，显著增加了早期增殖和双皮质素（DCX）阳性细胞的有丝分裂后阶段，而 SD 期间给予莫达非尼治疗，与 SD+Vehicle 组相比，增加了 DCX 阳性细胞的中期和有丝分裂后阶段。睡眠剥夺后，BrdU 阳性细胞以及齿状回（DG）区的脑源性神经营养因子（BDNF）表达显著降低。咖啡因和莫达非尼均可显著改善 DG 区的 BDNF 表达。与 SD+Vehicle 组相比，莫达非尼而非咖啡因可显著降低 SD 期间海马腺苷水平。综上所述，SD 期间给予咖啡因或莫达非尼治疗可防止 SD 诱导的神经元增殖和分化下降。SD 期间 NCP 的咖啡因和莫达非尼诱导改变可能涉及 BDNF 和腺苷水平的调节。
