In mammals, the environmental light/dark cycle strongly synchronizes the circadian clock within the suprachiasmatic nuclei (SCN) to 24 hr. It is well known that not only photic but also nonphotic stimuli can entrain the SCN clock. Actually, many studies have shown that a daytime injection of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH DPAT), a serotonin 1A/7 receptor agonist, as a nonphotic stimulus induces phase advances in hamster behavioral circadian rhythms in vivo, as well as the neuron activity rhythm of the SCN in vitro. Recent reports suggest that mammalian homologs of the Drosophila clock gene, Period (Per), are involved in photic entrainment. Therefore, we examined whether phase advances elicited by 8-OH DPAT were associated with a change of Period mRNA levels in the SCN. In this experiment, we cloned partial cDNAs encoding hamster Per1, Per2, and Per3 and observed both circadian oscillation and the light responsiveness of Period. Furthermore, we found that the inhibitory effect of 8-OH DPAT on hamster Per1 and Per2 mRNA levels in the SCN occurred only during the hamster's mid-subjective day, but not during the early subjective day or subjective night. The present findings demonstrate that the acute and circadian time-dependent reduction of Per1 and/or Per2 mRNA in the hamster SCN by 8-OH DPAT is strongly correlated with the phase resetting in response to 8-OH DPAT.

No abstract

Nerve growth factor (NGF) plays an important role in the survival and maintenance of cholinergic neurons in the central neuronal system. Since this factor does not cross the blood-brain barrier and is easily metabolized by peptidases when administered peripherally, it can be used for medical treatment only when directly injected into the brain. We report here that repeated oral administration of the stimulators for the NGF synthesis, idebenone and propentofylline, produced a significant recovery of the reduced NGF content in the frontal and parietal cortices of aged rats. These compounds also improved deficits of performance in water maze, passive avoidance and habituation tasks in basal-forebrain-lesioned rats. These results suggest that the use of the stimulators for the NGF synthesis may provide a therapeutic approach to cholinergic dysfunction.

No abstract

No abstract