Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK, 99775-7000, USA.
Psychopharmacology (Berl). 2010 Apr;209(3):217-24. doi: 10.1007/s00213-010-1778-y. Epub 2010 Feb 26.
Evidence links longevity to dietary restriction (DR). A decrease in body temperature (T(b)) is thought to contribute to enhanced longevity because lower T(b) reduces oxidative metabolism and oxidative stress. It is as yet unclear how DR decreases T(b).
Here, we test the hypothesis that prolonged DR decreases T(b) by sensitizing adenosine A(1) receptors (A(1)AR) and adenosine-induced cooling.
Sprague-Dawley rats were dietary restricted using an every-other-day feeding protocol. Rats were fed every other day for 27 days and then administered the A(1)AR agonist, N(6)-cyclohexyladenosine (CHA; 0.5 mg/kg, i.p.). Respiratory rate (RR) and subcutaneous T(b) measured using IPTT-300 transponders were monitored every day and after drug administration. DR animals displayed lower RR on day 20 and lower T(b) on day 22 compared to animals fed ad libitum and displayed a larger response to CHA. In all cases, RR declined before T(b). Contrary to previous reports, a higher dose of CHA (5 mg/kg, i.p.) was lethal in both dietary groups. We next tested the hypothesis that sensitization to the effects of CHA was due to increased surface expression of A(1)AR within the hypothalamus. We report that the abundance of A(1)AR in the membrane fraction increases in hypothalamus, but not cortex of DR rats.
These results suggest that every-other-day feeding lowers T(b) via sensitization of thermoregulatory effects of endogenous adenosine by increasing surface expression of A(1)AR.
Evidence that diet can modulate purinergic signaling has implications for the treatment of stroke, brain injury, epilepsy, and aging.
有证据表明长寿与饮食限制（DR）有关。体温（T(b)）降低被认为有助于延长寿命，因为较低的 T(b) 会降低氧化代谢和氧化应激。目前尚不清楚 DR 如何降低 T(b)。
本研究旨在通过敏化腺苷 A(1)受体（A(1)AR）和腺苷诱导的冷却来检验 DR 通过降低 T(b)从而延长寿命的假说。
使用隔日喂养方案对 Sprague-Dawley 大鼠进行饮食限制。大鼠每隔一天喂食 27 天，然后给予 A(1)AR 激动剂 N(6)-环已基腺苷（CHA；0.5 mg/kg，腹腔注射）。使用 IPTT-300 应答器监测每天和给药后的呼吸频率（RR）和皮下 T(b)。DR 动物在第 20 天显示出较低的 RR，在第 22 天显示出较低的 T(b)，并且对 CHA 的反应更大。在所有情况下，RR 都先于 T(b)下降。与之前的报告相反，两种饮食组中更高剂量的 CHA（5 mg/kg，腹腔注射）都是致命的。我们接下来测试了这样一个假设，即对 CHA 作用的敏化是由于下丘脑内 A(1)AR 的表面表达增加所致。我们报告说，DR 大鼠下丘脑而不是皮层中的 A(1)AR 膜部分的丰度增加。
这些结果表明，隔日喂养通过增加 A(1)AR 的表面表达来敏化内源性腺苷的体温调节作用，从而降低 T(b)。
饮食可以调节嘌呤能信号的证据对中风、脑损伤、癫痫和衰老的治疗具有重要意义。
