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

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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