Vazquez Jacqueline, Hall Steven C, Greco Mary Ann
Behavioral Biochemistry Laboratory, Biosciences Division, SRI International, 333 Ravenswood Ave., Menlo Park, CA 94025, USA.
Brain Res. 2009 Nov 17;1298:37-45. doi: 10.1016/j.brainres.2009.08.064. Epub 2009 Aug 31.
Age-related changes in brain function include those affecting learning, memory, and sleep-wakefulness. Sleep-wakefulness is an essential behavior that results from the interaction of multiple brain regions, peptides, and neurotransmitters. The biological function(s) of sleep, however, remains unknown due to a paucity of information available at the cellular level. Aged rats exhibit alterations in the circadian and homeostatic influences associated with sleep-wake regulation. We recently showed that alterations in cortical profiles occur after timed bouts of spontaneous sleep in young rats. Examination of the cellular response to sleep-wake in old rats may thus provide insight(s) into the biological function(s) of sleep. To test this hypothesis, we monitored cortical profiles in the frontal cortex of young and old Sprague-Dawley rats after timed bouts of spontaneous sleep-wake behavior. Proteins were separated by two-dimensional electrophoresis (2-DE), visualized by fluorescent staining, imaged, and analyzed as a function of behavioral state and age. Old rats showed a 6-fold increase in total protein expression, independent of the behavioral state at sacrifice. When analyzed according to age and behavioral state, there was a decrease (approximately 46%) in the number of phospho-spots present during SWS in aged animals. SWS-associated spots present only in old animals were associated with multiple functions including vesicular transport, cell signaling, oxidation state, cytoskeletal support, and energy metabolism. These data suggest that the intracellular response to the signaling associated with spontaneous sleep is affected by age and is consistent with the idea that the ability of sleep to fulfill its function(s) may become diminished with age.
与年龄相关的脑功能变化包括那些影响学习、记忆和睡眠-觉醒的变化。睡眠-觉醒是一种重要行为,它是由多个脑区、肽和神经递质相互作用产生的。然而,由于细胞水平上可用信息的匮乏,睡眠的生物学功能仍然未知。老年大鼠在与睡眠-觉醒调节相关的昼夜节律和稳态影响方面表现出改变。我们最近发现,幼鼠在定时自发睡眠后,皮质特征会发生变化。因此,研究老年大鼠对睡眠-觉醒的细胞反应可能有助于深入了解睡眠的生物学功能。为了验证这一假设,我们在幼龄和老龄Sprague-Dawley大鼠进行定时自发睡眠-觉醒行为后,监测其额叶皮质的皮质特征。蛋白质通过二维电泳(2-DE)分离,用荧光染色可视化,成像,并根据行为状态和年龄进行分析。老年大鼠的总蛋白表达增加了6倍,与处死时的行为状态无关。根据年龄和行为状态分析时,老年动物慢波睡眠期间磷酸化斑点的数量减少(约46%)。仅在老年动物中出现的与慢波睡眠相关的斑点与多种功能有关,包括囊泡运输、细胞信号传导、氧化状态、细胞骨架支持和能量代谢。这些数据表明,与自发睡眠相关的信号的细胞内反应受年龄影响,这与睡眠履行其功能的能力可能随年龄增长而减弱的观点一致。