Effects of leptin on proliferation of astrocyte- and tanycyte-like neural stem cells in the adult mouse medulla oblongata.

Astrocyte- and tanycyte-like neural stem cells (NSCs) were recently detected in the area postrema (AP) and central canal (CC) of the adult medulla oblongata, respectively. The present study aimed to examine dynamical behaviors of the astrocyte- and tanycyte-like NSCs of the mouse medulla oblongata to leptin. The neurosphere assay identified astrocytes in the AP and tanycytes in the CC as NSCs based on their self-renewing neurospherogenic potential. Both NSCs in neurosphere cultures were multipotent cells that generate astrocytes, oligodendrocytes, and neurons. Astrocyte-like NSCs actively proliferated and tanycyte-like NSCs were quiescent under physiologically-relevant in vivo conditions. Chronic leptin treatment promoted proliferation of astrocyte-like NSCs in the AP both in vitro and in vivo. Leptin receptors were expressed in astrocyte-like, but not tanycyte-like NSCs. Food deprivation significantly diminished proliferation of astrocyte-like NSCs. Therefore, the present study indicates that proliferation of astrocyte-like, but not tanycyte-like NSCs is regulated by nutritional conditions.

Chronic running and a corticosterone treatment attenuate astrocyte-like neural stem cell proliferation in the area postrema of the adult mouse brain.

The discovery of neural stem cells (NSCs) in the adult mammalian brain has provided insights into an extra level of brain plasticity. The proliferation and differentiation of NSCs is modulated by various physiological, pathological, and pharmacological stimuli. NSCs were recently detected in the medulla oblongata of adult rodents and humans; however, their functional significance currently remains unknown. In the present study, we examined the effects of chronic wheel-running and a corticosterone (CORT) treatment on the proliferation of astrocyte-like NSCs in the area postrema (AP) and dentate gyrus (DG). Chronic running significantly decreased the number of bromodeoxyuridine (BrdU)-labeled astrocyte-like NSCs in the AP of adult mice, but markedly increased that of BrdU+ NSCs/neural progenitor cells in the DG. The chronic CORT treatment markedly reduced the number of BrdU+ astrocyte-like NSCs in the AP, but not in the DG. These results demonstrate that the proliferation of astrocyte-like NSCs in the medulla oblongata is decreased by chronic running and a CORT treatment.

Neural stem cell phenotype of tanycyte-like ependymal cells in the circumventricular organs and central canal of adult mouse brain.

Tanycyte is a subtype of ependymal cells which extend long radial processes to brain parenchyma. The present study showed that tanycyte-like ependymal cells in the organum vasculosum of the lamina terminalis, subfornical organ and central canal (CC) expressed neural stem cell (NSC) marker nestin, glial fibrillar acidic protein and sex determining region Y. Proliferation of these tanycyte-like ependymal cells was promoted by continuous intracerebroventricular infusion of fibroblast growth factor-2 and epidermal growth factor. Tanycytes-like ependymal cells in the CC are able to form self-renewing neurospheres and give rise mostly to new astrocytes and oligodendrocytes. Collagenase-induced small medullary hemorrhage increased proliferation of tanycyte-like ependymal cells in the CC. These results demonstrate that these tanycyte-like ependymal cells of the adult mouse brain are NSCs and suggest that they serve as a source for providing new neuronal lineage cells upon brain damage in the medulla oblongata.

Chemical synthesis of homogeneous human glycosyl-interferon-ß that exhibits potent antitumor activity in vivo.

Chemical synthesis of homogeneous human glycoproteins exhibiting bioactivity in vivo has been a challenging task. In an effort to overcome this long-standing problem, we selected interferon-ß and examined its synthesis. The 166 residue polypeptide chain of interferon-ß was prepared by covalent condensation of two synthetic peptide segments and a glycosylated synthetic peptide bearing a complex-type glycan of biological origin. The peptides were covalently condensed by native chemical ligation. Selective desulfurization followed by deprotection of the two Cys(Acm) residues gave the target full-length polypeptide chain of interferon-ß bearing either a complex-type sialyl biantennary oligosaccharide or its asialo form. Subsequent folding with concomitant formation of the native disulfide bond afforded correctly folded homogeneous glycosyl-interferon-ß. The chemically synthesized sialyl interferon-ß exhibited potent antitumor activity in vivo.