Abstract:
As the central regulatory system of an organism, the brain is responsible for overseeing a wide variety of physiological processes essential for an organism\'s survival. To maintain the environment necessary for neurons to function, the brain requires highly selective uptake and elimination of specific molecules through the blood-brain barrier (BBB). As an organism\'s activities vary throughout the day, how does the BBB adapt to meet the changing needs of the brain? A mechanism is through temporal regulation of BBB permeability via its circadian clock, which will be the focal point of this chapter. To comprehend the circadian clock\'s role within the BBB, we will first examine the anatomy of the BBB and the transport mechanisms enabling it to fulfill its role as a restrictive barrier. Next, we will define the circadian clock, and the discussion will encompass an introduction to circadian rhythms, the Transcription-Translation Feedback Loop (TTFL) as the mechanistic basis of circadian timekeeping, and the organization of tissue clocks found in organisms. Then, we will cover the role of the circadian rhythms in regulating the cellular mechanisms and functions of the BBB. We discuss the implications of this regulation in influencing sleep behavior, the progression of neurodegenerative diseases, and finally drug delivery for treatment of neurological diseases.
摘要:
作为生物体的中央调控系统,大脑负责监督生物体生存所必需的各种生理过程。为了维持神经元发挥作用所必需的环境,大脑需要通过血脑屏障(BBB)高度选择性地摄取和消除特定分子。由于生物体的活动在一天中各不相同,血脑屏障如何适应大脑不断变化的需求?一种机制是通过昼夜节律对血脑屏障通透性进行时间调节,这将是本章的重点。为了理解生物钟在血脑屏障中的作用,我们将首先检查BBB的解剖结构和运输机制,使其能够发挥其作为限制性屏障的作用。接下来,我们将定义生物钟,讨论将包括对昼夜节律的介绍,转录-翻译反馈环(TTFL)作为昼夜节律计时的机制基础,以及在生物体中发现的组织钟的组织。然后,我们将介绍昼夜节律在调节BBB的细胞机制和功能中的作用。我们讨论了这种调节对影响睡眠行为的影响,神经退行性疾病的进展,最后是治疗神经系统疾病的药物递送。