School of Psychology & Public Health, La Trobe University, Melbourne, VIC, Australia; Centre for Respiratory Science & Health, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia.
School of Psychology & Public Health, La Trobe University, Melbourne, VIC, Australia.
Behav Brain Res. 2024 Feb 4;457:114715. doi: 10.1016/j.bbr.2023.114715. Epub 2023 Oct 12.
Calorie restriction (CR) has been shown to extend the mean and maximum lifespan in both preclinical and clinical settings. We have previously demonstrated that CR attenuates lipopolysaccharide (LPS)-induced fever and sickness behavior. CR also leads to reductions in pro-inflammatory and increases in anti-inflammatory profiles. LPS is a bacterial mimetic; however, few studies have explored this phenomenon utilizing a viral mimetic, such as polyinosinic:polycytidylic acid (poly I:C). Dose-dependently, poly I:C induced an increase in core body temperature (T), with the largest dose (5000 µg/kg) resulting in a 1.62 °C ( ± 0.23 °C) T increase at 7 h post-injection in ad libitum mice and was associated with reduced home-cage locomotor activity. We then investigated the effect of 50% CR for 28 days to attenuate fever and sickness behavior induced by a poly I:C (5000 µg/kg) viral immune challenge. CR resulted in the partial attenuation of fever and sickness behavior measures post-poly I:C. The freely fed, control mice demonstrated a 2.02 °C ( ± 0.22 °C) increase in T at 7 h post-injection compared to the CR poly I:C group which demonstrated an increase in T of 0.94 °C ( ± 0.27 °C). Locomotor patterns post-injection were different, CR mice displayed a reduction in activity during the light phase, and the control group displayed a reduction during the dark phase. CR moderately attenuated the neuroinflammatory response with a reduction in microglial density in the ventromedial nucleus of the hypothalamus. The fever and sickness behavior attenuation seen after CR may be driven by similar anti-inflammatory processes as after LPS; however, further investigation is required.
热量限制（CR）已被证明可延长临床前和临床环境中的平均和最大寿命。我们之前已经证明，CR 可减轻脂多糖（LPS）引起的发热和疾病行为。CR 还导致促炎因子减少和抗炎因子增加。LPS 是一种细菌模拟物；然而，很少有研究利用病毒模拟物（如多聚肌苷酸：多聚胞苷酸（poly I:C））来探索这种现象。poly I:C 剂量依赖性地引起核心体温（T）升高，最大剂量（5000μg/kg）在自由喂养的小鼠中导致注射后 7 小时 T 升高 1.62°C（±0.23°C），并与减少笼内运动活动有关。然后，我们研究了 50% CR 28 天的作用，以减轻 poly I:C（5000μg/kg）病毒免疫挑战引起的发热和疾病行为。CR 导致 poly I:C 后发热和疾病行为测量值部分减轻。与 CR poly I:C 组相比，自由喂养的对照组在注射后 7 小时 T 升高 2.02°C（±0.22°C），而 CR poly I:C 组 T 升高 0.94°C（±0.27°C）。注射后运动模式不同，CR 小鼠在光照期活动减少，对照组在暗期活动减少。CR 通过减少下丘脑腹内侧核中小胶质细胞密度，适度减轻神经炎症反应。CR 后观察到的发热和疾病行为减轻可能是由类似的抗炎过程驱动的，但是需要进一步研究。
