Circadian disruption of hippocampus in an early senescence male mouse model.
Circadian disruption of hippocampus in an early senescence male mouse model.
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DOI：
10.1016/j.pbb.2022.173388
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发表时间：
2022-06
影响因子：
3.6
通讯作者：
Gamble, Karen L.
中科院分区：
文献类型：
--
作者：
Davis, Jennifer A.;Paul, Jodi R.;Mokashi, Mugdha V.;Yates, Stefani A.;Mount, Daniel J.;Munir, Hira A.;Goode, Lacy K.;Young, Martin E.;Allison, David B.;Gamble, Karen L.
随着人类平均寿命的延长，与年龄相关的认知能力下降和昼夜节律紊乱正在成为日益严重的问题。衰老加速小鼠（SAM）的多个品系表现出寿命缩短，特别是SAMP8品系已被充分证明表现出行为认知缺陷以及昼夜节律运动活动的双峰模式。然而，对这些小鼠海马体内的昼夜节律调节知之甚少。在这里，我们验证了一个假设，即在这个早期衰老模型中，SAMP8动物分子生物钟的破坏导致了行为和生理的破坏。我们发现SAMP8动物的SCN中PER2蛋白表达在4个月时正常，尽管在这个年龄存在中断的轮跑活动节律。有趣的是，在SAMP8动物的海马中没有观察到PER2表达的显著节律，尽管在SAMR1对照中有显著的24小时节律。我们还研究了限时进食作为拯救受损海马可塑性的潜在策略。与SAMR1对照相比，限时喂养增加了SAMP8小鼠的Schaffer侧侧- ca1突触的长期增强。总的来说，我们在这个早期衰老模型（早在4个月）中证实了昼夜运动节律的破坏，并发现这种破坏不是由于SCN中PER2水平的不规律；然而，其他scn外的昼夜节律振荡器（即海马体）可能随着衰老的加速而受损。
Age-related cognitive decline and disruptions in circadian rhythms are growing problems as the average human life span increases. Multiple strains of the senescence-accelerated mouse (SAM) show reduced life span, and the SAMP8 strain in particular has been well documented to show cognitive deficits in behavior as well as a bimodal pattern of circadian locomotor activity. However, little is known about circadian regulation within the hippocampus of these strains of mice. Here we test the hypothesis that in this early senescence model, disruption of the molecular circadian clock in SAMP8 animals drives disrupted behavior and physiology. We found normal rhythms in PER2 protein expression in the SCN of SAMP8 animals at 4 months, despite the presence of disrupted wheel-running activity rhythms at this age. Interestingly, a significant rhythm in PER2 expression was not observed in the hippocampus of SAMP8 animals, despite a significant 24-h rhythm in SAMR1 controls. We also examined time-restricted feeding as a potential strategy to rescue disrupted hippocampal plasticity. Time-restricted feeding increased long-term potentiation at Schaffer collateral-CA1 synapses in SAMP8 mice (compared to SAMR1 controls). Overall, we confirm disrupted circadian locomotor rhythms in this early senescence model (as early as 4 months) and discovered that this disruption is not due to arrhythmic PER2 levels in the SCN; however, other extra-SCN circadian oscillators (i.e., hippocampus) are likely impaired with accelerated aging.
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影响因子：
29
作者：
Chaix A;Lin T;Le HD;Chang MW;Panda S
通讯作者：
Panda S
影响因子：
4.8
作者：
Lv C;Ma Q;Han B;Li J;Geng Y;Zhang X;Wang M
通讯作者：
Wang M
影响因子：
4.2
作者：
Lopez-Ramos, Juan Carlos;Jurado-Parras, Maria Teresa;Delgado-Garcia, Jose M.
通讯作者：
Delgado-Garcia, Jose M.
影响因子：
13.1
作者：
Manoogian ENC;Panda S
通讯作者：
Panda S
DOI：
10.1523/jneurosci.0451-11.2011
发表时间：
2011-07-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Nakamura TJ;Nakamura W;Yamazaki S;Kudo T;Cutler T;Colwell CS;Block GD
通讯作者：
Block GD