Though melatonin has a wide variety of biological functions, its effects on the neural stem cells (NSCs) is still unknown. In this study, we examined the effects of melatonin at either physiological (0.01-10 nm) or pharmacological concentrations (1-100 microM) on the proliferation and neural and astroglial differentiation of NSCs derived from the mouse embryo striatum using an in vitro culture system. We found that melatonin at pharmacological concentrations, but not at physiological concentrations, suppressed epidermal growth factor (EGF)-stimulated NSC proliferation (increment of viable cells, DNA synthesis and neurosphere formation) in a concentration-dependent manner. Furthermore, treatment with melatonin at a pharmacological concentration during the proliferation period facilitated 1% FBS-induced neural differentiation of NSCs without affecting the astroglial differentiation. In contrast, the treatment with melatonin at pharmacological concentrations during the differentiation period decreased the neural differentiation of the NSCs. As with melatonin, MCI-186, an antioxidant, suppressed EGF-stimulated NSC proliferation and facilitated the subsequent neural differentiation of NSCs. These results suggest that melatonin exerts potent modulatory effects on NSC functions including the suppression of the proliferation and facilitation of neuronal differentiation, likely via its antioxidant activity. As neurogenesis is thought to play an important role in ameliorating the deficit in neurodegenerative diseases, melatonin might be beneficially used for the treatment diseases such as cerebral infarction.

Epidermal growth factor-responsive neural precursor cells were used as donor cells for transplantation into wild-type and myelin-deficient shiverer (shi) mice. The cells engrafted robustly within the CNS following intracerebroventricular and cisternal transplantation in neonatal mice. The cells adopted glial phenotypes, and some functioned as oligodendrocytes, producing myelin basic protein and morphologically normal internodal myelin sheaths. When individual shi mice received two transplants (on post-natal days 1 and 3), donor-derived cells disseminated widely and expressed myelin basic protein in central white matter tracts throughout the brain.

No abstract

Secretory immunoglobulin A (S-IgA) plays the major role for protecting mucosal tissue from infection, and its level in saliva is thought to be the indicator of immune function in the oral cavity. In the present study, we measured the levels of S-IgA, cortisol and total protein in whole saliva as well as flow rate in healthy young adults (n‫)8ס‬ throughout a 24-hr period, and found that salivary S-IgA, cortisol and flow rate fluctuated in a circadian manner with their acrophases (peak time of the rhythms) at 06:50h, 09:04 h and 19.01h, respectively (PϽ0.05). Mesor (midline estimating statistics of rhythm) of the three rhythms was 0.30 mg/ml for S-IgA, 8.56 ng/ml for cortisol, and 0.47 ml/min for the flow rate. The acrophase of S-IgA rhythm corresponded to the nadir of the flow rate rhythm, indicating that these two rhythms are anti-phase to each other. We suggest that the circadian rhythm of S-IgA is not simply subject to daily fluctuation of the volume of salivary fluid that dilutes S-IgA, but is influenced directly or indirectly by central circadian pacemaker, because the ratio of S-IgA to total protein in the morning is more than 3 times higher than that in the evening. The elevation of S-IgA concentration in saliva from midnight to early morning may indicate compensatory mechanism of oral immune system to the fall of saliva secretion during sleep. rate declines to nearly zero level during sleep 3). It is well known that the nocturnal fall of saliva secretion reduces mechanical washing in the oral cavity and increases susceptibility to dental caries. One of the most important indicators of local immune system in the oral cavity is secretory immunoglobulin A (S-IgA), which can reduce the adherence of microorganisms to the tooth surface and oral mucosa 7,8). It has also been stated that S-IgA plays a significant role in maintaining homeostasis in oral microbial populations 7). A recent study has demonstrated that the concentration of S-IgA in saliva changes rapidly after awakening; S-IgA is remarkably high at the time of awakening and falls subsequently 9). The S-IgA decline is correlated with