An animal model study of vitamin B12 for elucidation of its effectiveness in circadian rhythm disorders.

据报道，维生素B12(甲钴胺)对非24小时睡眠-觉醒综合征和睡眠相延迟综合征有效。为了寻找VB12可能的时间生物学作用，比较了高VB12状态和低VB12状态下大鼠昼夜节律的自由跑动期(Tau)和昼夜节律系统对光的敏感性。研究VB12在恒定条件下对tau的影响。比较高VB12和低VB12两种血清状态下大鼠在恒定暗红光条件下，轮子跑、运动和饮酒的昼夜节律的自由奔跑周期。在血清高VB12状态时，自由跑动期有时缩短。然而，总的来说，在血清高VB12状态和低VB12状态之间，没有发现自由运行期的显著差异。Mecobalam…用VB12缺乏的食物喂养100天的失明大鼠，皮下注射更多的IN，持续2周。甲钴胺输注后血清VB12水平明显升高，自由运动期略有缩短，但差异显著。然而，这种缩短效应是值得怀疑的，因为在自由奔跑期有逐渐减少的趋势，可能是由于大鼠的年龄增长。VB12对昼夜节律系统光敏感性的影响：在对光脉冲(700lux，30min)的相位响应曲线中，血清低VB12状态的延迟部分与超前部分的比率大于血清高VB12状态。在血清高VB12状态下，昼夜行为节律恢复到急性6小时噬菌体前进所需的天数显著短于血清低VB12状态下。在12：12小时的明暗周期中，光照强度从5勒克斯逐步降低到0.02勒克司。大鼠行为的昼夜节律在高、低VB12状态下均可进入0.02lux的明暗周期，提示VB12(甲钴胺)可增强大鼠昼夜节律对光的敏感性，有时可缩短昼夜行为节律的自由运行周期。这些发现可能解释了VB12在昼夜节律紊乱中的作用机制。较少

Vitamin B12 (mecobalamin) has been reported to be effective for non-24-hour sleep-wake syndrome and delayed sleep phase syndrome. In search of possible chronobiological actions of VB12, the free-running period (tau) of rat circadian rhythm and the sensitivity of the circadian system to light were compared between serum high and low VB12 states, which were made by feeding rats with a VB12-rich chow (1 mg/kg) and a VB12-deficient chow, respectively.1. The effect of VB12 on tau under constant conditions.The free-running periods of the circadian rhythms of wheel-running, locomotor and drinking activities under constant dim red light conditions were compared between serum high and low VB12 states, which were made by feeding rats with the VB12-rich and -deficient chows, respectively. The free-running period was sometimes shortened during serum high VB12 state. As a whole, however, no significant difference in the free-running period was found between serum high and low VB12 states. Mecobalam … More in was subcutaneously infused for 2 weeks to the blinded rats fed with the VB12-deficient chow for 100 days. The mecobalamin infusion produced a marked increase in serem VB12 level, and shortened slightly but significantly the free-running period. However, this shortening effect is doubtful, because there was a gradually decreasing trend in the free-running period, possibly due to rats' aging.2. The effects of VB12 on the sensitivity of the circadian system to light.In the phase response curve to light pulses (700 lux, 30 min), the ratio of the delay portion to the advance portion was greater in serum low VB12 state than in serum high VB12 state. The number of days required for the reentraiment of circadian behavioral rhythm to an acute 6-hour phage advance was significantly shorter in the serum high VB12 state than in serum low VB12 state. The light intensity during a 12 : 12 hour light-dark cycle was stepwise decreased from 5 to 0.02 lux. The circadian rhythm of rat behavior could entrain to the light-dark cycle of 0.02 lux both in serum high and low VB12 states.These results suggest that VB12 (mecobalamin) enhances the sensitivity of the rat circadian system to light, and sometimes shortens the free-running period of circadian behavioral rhythm. These findings may explain the mechanisms underlying the effectiveness of VB12 in the circadian rhythm disorders. Less