A causal role for brain-derived neurotrophic factor in the homeostatic regulation of sleep
A causal role for brain-derived neurotrophic factor in the homeostatic regulation of sleep
复制标题
DOI：
10.1523/jneurosci.5510-07.2008
复制
发表时间：
2008-04-09
影响因子：
5.3
通讯作者：
Cirelli, Chiara
中科院分区：
文献类型：
--
作者：
Faraguna, Ugo;Vyazovskiy, Vladyslav V.;Cirelli, Chiara
慢波活动 (SWA)，即非快速眼动 (NREM) 睡眠期间 0.5 至 4 Hz 之间的 EEG 功率，是睡眠需求的最佳表征标志之一，因为它随着之前清醒持续时间的变化而增加，并在睡眠期间减少，但其潜在机制仍不清楚。我们假设 SWA 在睡眠开始时较高，因为它反映了在前一个清醒时期皮质和皮质下区域广泛突触增强的发生情况。与这一假设相一致的是，我们最近表明，大鼠探索的次数越多，清醒期间 BDNF 的皮质表达越强，并且在随后的睡眠期间 SW 的增加越大。有令人信服的证据表明 BDNF 在突触增强中起着因果作用，体内外源性应用 BDNF 足以诱导突触强度的长期增强。因此，我们对清醒大鼠进行皮质单侧显微注射 BDNF，并在随后的睡眠期间测量 SWA。相对于对侧半球，非快速眼动睡眠期间注射半球的 SWA 较高。该效应在 2 小时内可逆转，并且在清醒或快速眼动睡眠期间不会发生。注射媒介物后，NREM SWA 中的不对称性并未发生。此外，在清醒期间显微注射多克隆抗 BDNF 抗体或 K252a（BDNFTrkB 受体抑制剂）会导致随后睡眠期间局部 SWA 减少。这些影响也是可逆的并且是 NREM 睡眠所特有的。这些结果显示了清醒期间 BDNF 表达与随后的睡眠调节之间的因果关系。
Slow-wave activity ( SWA), the EEG power between 0.5 and 4 Hz during non- rapid eye movement ( NREM) sleep, is one of the best characterized markers of sleep need, because it increases as a function of preceding waking duration and decreases during sleep, but the underlying mechanisms remain unknown. Wehypothesized thatSWAis high at sleep onset because it reflects the occurrence, during the previous waking period, of widespread synaptic potentiation in cortical and subcortical areas. Consistent with this hypothesis, we recently showed that the more rats explore, the stronger is the cortical expression of BDNF during wakefulness, and the larger is the increase inSWAduring the subsequent sleep period. There is compelling evidence that BDNF plays a causal role in synaptic potentiation, and exogenous application of BDNF in vivo is sufficient to induce long- term increases in synaptic strength. We therefore performed cortical unilateral microinjections of BDNF in awake rats and measured SWA during the subsequent sleep period. SWA during NREM sleep was higher in the injected hemisphere relative to the contralateral one. The effect was reversible within 2 h, and did not occur during wakefulness or rapid eye movement sleep. Asymmetries in NREM SWA did not occur after vehicle injections. Furthermore, microinjections, during wakefulness, of a polyclonal anti- BDNF antibody or K252a, an inhibitor ofBDNFTrkB receptors, led to a localSWAdecrease during the following sleep period. These effects were also reversible and specific forNREMsleep. These results show a causal link between BDNF expression during wakefulness and subsequent sleep regulation.