Studies of active substances and action mechanisms of traditional Japanese medicines on anosmia, olfactory disturbance, using olfactory bulb lesioned mice.

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Reduction of olfactory sense is one of the symptoms of senile dementia of the Alzheimer type(SDAT). Some researchers hypothesize that changes in the olfactory system are not only a symptom but also a cause for SDAT, but little is known about the correlation between olfactory sense and memory. In animal experiments, a reduction of memory maintenance has been reported in rats after olfactory bulbectomy. The role of the olfactory bulb in rodents is related to exchange of information, sex instinct and emotion caused by odor. The olfactory bulb is not only an organ of smell but is also related to emotional behavior.Spraying zinc sulfate into the nasal cavity promotes the secretion of glutamate, so that the sense of smell is definitely induced by obstruction of the regeneration of olfactory bulb epithelial cells. In the experiments until now, reductions of learning memory and of the neurotransmitters in the brain were observed to be induced by zinc sulfate.We investigated the effects of Kampo formulation, Kamishoyosan, on changes of neurotransmitters and reduction of learning memory in mice with olfactory bulb lesioned mice. Kamishoyosan extract was administered orally and an improvement in learning memory and reversal of the decrease of neurotransmitters in the brain were observed. It is therefore suggested that Kamishoyosan may improve learning memory repairing the injury to the neurons and restoring the amount of neurotransmitters. And we observed the behavioral change under systemic administration of L-carnosine(β-alanyl-L-histidine) in mice, and L-carnosine causes stereotyped behavior which is dependent on dopaminergic transmission. Furthermore, administration of nomifensine, dopamine reuptake inhibitor, before zinc sulfate irrigation significantly protected the occurrence of acquisition impairment.