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Optic nerve stimulation has been reported to evoke a field potential (FP) in rat suprachiasmatic nucleus (SCN) slices. Methylcobalamin,δ-(5,6-dymethylbenzimidazoyl)-Co-methyl-cobamide (Me-B 12 ) enhanced this FP and the enhancement lasted more than 1 h after washing out. Maximal enhancement (143.6±9.8%) was achieved at a concentration of 10 μM. By contrast, cyanocobalamin containing CN- instead of CH 3 -showed no enhancement of the amplitude in the FP. Me-B 12 induced enhancement of FP was strongly blocked by an N -methyl- d -aspartate (NMDA) receptor antagonist, dl -2-amino-5-phosphonovaleric acid (APV). These results indicate that CH 3 - in the Me-B 12 is required to modulate the FP amplitude and the NMDA receptor is involved in the long-lasting FP enhancement induced by Me-B 12 . The present results suggest that Me-B 12 modifies the photic entrainment of the circadian clock in the suprachiasmatic nucleus via an activation of NMDA receptors.

Methylcobalamin (CH3-B12) enhanced postsynaptic field potential (PSP) elicited from hippocampal slices (around 180% at a maximum), lasting more than 1 h after washing out, while it had no effect on antidromic spike potential (AP). By contrast, cyanocobalamin containing CN- instead of CH3- showed no enhancement in the PSP amplitude, suggesting that CH3- plays an important role for the PSP enhancement by methylcobalamin. The treatment with N-methyl-D-aspartate (NMDA) receptor specific antagonist, DL-2-amino-5-phosphonovaleric acid (APV) inhibited methylcobalamin-induced PSP enhancement by 50%, suggesting that NMDA receptor is partially relevant to the formation of this enhancement. Glutamate release from electrically stimulated slices was not enhanced by the treatment with methylcobalamin, suggesting that methylcobalamin affects the postsynaptic sites in hippocampal neurons. In whole cell voltage clamp recordings using cultured hippocampal neurons, methylcobalamin increased the currents elicited by NMDA time-dependently. These results may indicate that CH3- is required to modulate the PSP amplitude at the postsynaptic site and at least, NMDA receptor is involved in the formation of long-lasting PSP potentiation induced by methylcobalamin.

Using optical recording techniques, we examined whether nitric oxide (NO) is implicated in the impairment of the activity of hippocampal CA1 neurons induced by mild heat stress. A temperature increase from 32 to 38 °C reversibly depressed the neuronal activity in hippocampal slices. l -Arginine (1 mM), an NO donor, enhanced the heat-induced depression of the activity of hippocampal CA1 neurons. N ω -Nitro- l -arginine methyl ester, an inhibitor of nitric oxide synthase, attenuated the inhibition of the neuronal activity induced by a temperature increase. Methylcobalamin (10 μM), a vitamin B 12 analogue that reduces NO production, reduced the heat-induced depression of the neuronal activity. These results suggest that NO contributes, at least in part, to the heat-induced depression of the neuronal activity in the hippocampal CA1 region.

We examined the effects of methylcobalamin (methyl-B12, mecobalamin) on degeneration of motor nerve terminals in the anterior gracile muscle of gracile axonal dystrophy (GAD) mutant mice. GAD mice received orally methyl-B12 (1 mg/kg body wt/day) from the 40th day after birth for 25 days. In the distal endplate zone of the muscle, although most terminals were degenerated in both the untreated and methyl-B12-treated GAD mice, sprouts were more frequently observed in the latter. In the proximal endplate zone, where few degenerated terminals were seen in both groups of the mice, the perimeter of the terminals was increased and the area of the terminals was decreased significantly in the methyl-B12-treated GAD mice. These findings indicate that methyl-B12 promotes regeneration of degenerating nerve terminals in GAD mice.

Eight young males were subjected to a single blind cross-over test to see the effects of vitamin B12 (methylcobalamin; VB12) on the phase-response of the circadian melatonin rhythm to a single bright light exposure. VB12 (0.5 mg/day) or vehicle was injected intravenously at 1230 h for 11 days, which was followed by oral administration (2 mg x 3/day) for 7 days. A serial blood sampling was performed under dim light condition (less than 200 lx) and plasma melatonin rhythm was determined before and after a single bright light exposure (2500 lx for 3 h) at 0700 h. The melatonin rhythm before the light exposure showed a smaller amplitude in the VB12 trial than in the placebo. The light exposure phase-advanced the melatonin rhythm significantly in the VB12 trail, but not in the placebo. These findings indicate that VB12 enhances the light-induced phase-shift in the human circadian rhythm.