東 森生

The intestinal-derived hormone motilin, a peptide belonging to the ghrelin family, induces strong gastric contractions and hunger sensations. However, whether motilin regulates food intake and its association with gastric motility remains unclear. Rodents are unsuitable for animal studies of motilin function, as both the motilin and motilin-receptor genes exist only as pseudogenes in their genomes. In this study, we investigated the role of motilin on food intake by simultaneously monitoring gastric contractions and their central mechanisms in the house musk shrew (Suncus murinus), a small mammal that produces motilin. In the interdigestive state, plasma motilin concentrations were elevated during spontaneous phase III contractions of the migrating motor complex (MMC) than during phase I contractions. Food intake during spontaneous phase III contractions was higher than that during phase I contractions. Intravenous motilin administration stimulated food intake during phase I, although its effect was weaker than that of ghrelin. Motilin-induced food intake was abolished in vagotomized suncus. Additionally, motilin increased c-Fos expression in tyrosine hydroxylase (TH) neurons in the area postrema and nucleus of the solitary tract of the brain stem, as well as in activated neuropeptide Y and TH neurons in the arcuate nucleus of the hypothalamus. These results revealed that motilin stimulated feeding linked to gastric motility through the vagus nerve and activated brain regions associated with food intake. Our findings provide evidence that motilin regulates food intake, highlighting its potential as a therapeutic strategy for appetite disorders.

White matter injury is caused by cerebral blood flow disturbances associated with stroke and demyelinating diseases such as multiple sclerosis. Remyelination is induced spontaneously after white matter injury, but progressive multiple sclerosis and white matter stroke are usually characterised by remyelination failure. However, the mechanisms underlying impaired remyelination in lesions caused by demyelination and stroke remain unclear. In the current study, we demonstrated that collagen fibres accumulated in the demyelinated lesions of multiple sclerosis patients (age range 23-80 years) and white matter lesions of stroke patients (age range 80-87 years), suggesting that the accumulation of collagen fibres correlates with remyelination failure in these lesions. To investigate the function of collagen fibres in the white matter lesions, we generated two types of white matter injury in mice. We induced focal demyelination by lysolecithin (LPC) injection and ischemic stroke by endothelin 1 (ET1) injection into the internal capsule. We found that type I collagen fibres were secreted in ET1-induced lesions with impaired white matter regeneration in the chronic phase of disease. We also showed that monocyte-derived macrophages that infiltrated into lesions from the peripheral blood produced type I collagen after white matter injury, and that type I collagen also exacerbated microglial activation, astrogliosis, and axonal injury. Finally, we demonstrated that oligodendrocyte differentiation and remyelination were inhibited in the presence of type I collagen after LPC-induced demyelination. These results suggest that type I collagen secreted by monocyte-derived macrophages inhibited white matter regeneration, and therefore, the modulation of type I collagen metabolism might be a novel therapeutic target for white matter injury.

In euryhaline teleosts, the cystic fibrosis transmembrane conductance regulator (CFTR) in seawater (SW)-type chloride cells facilitates apical Cl- secretion for SW adaptation, while alternative Cl- excretion pathways remain understudied. This study investigates the role of the calcium-activated chloride channel, Anoctamin 1 (ANO1), in the gills of the euryhaline Japanese medaka (Oryzias latipes) under hyperosmolality and cortisol (CORT) influence. Acclimation to artificial SW, NaCl, mannitol, or glucose significantly upregulated ANO1 and CFTR mRNA expression in gills, unlike urea treatment. In situ hybridization revealed ANO1 mRNA in chloride cells co-expressing CFTR and Na+, K+-ATPase under hyperosmotic conditions. ANO1 inhibition elevated plasma Cl- concentration, indicating impaired Cl- excretion. CORT or dexamethasone administration in freshwater (FW) fish significantly increased branchial ANO1 and CFTR mRNA expression, an effect attenuated by the glucocorticoid receptor (GR) antagonist RU486. Hyperosmotic treatment of isolated gill tissues rapidly induced ANO1 mRNA expression independent of CFTR mRNA changes, and this induction was unaffected by RU486. These findings highlight the dual regulation of ANO1 expression via hyperosmolality-induced cellular response and the CORT-GR system. Thus, branchial ANO1 may likely complement CFTR in Cl⁻ excretion, playing a key role in the hyperosmotic adaptation of euryhaline teleosts.

Abstract <p>Adult tissue stem cells of the anterior pituitary gland, CD9/SOX2-positive cells, are believed to exist in the marginal cell layer (MCL) bordering the residual lumen of the Rathke’s pouch. These cells migrate from the intermediate lobe side of the MCL (IL-MCL) to the anterior lobe side of the MCL and may be involved in supplying hormone-producing cells. Previous studies reported that some SOX2-positive cells of the anterior lobe differentiate into skeletal muscle cells. These findings suggest that CD9/SOX2-positive cells in the anterior pituitary have mesenchymal stem cell (MSC) properties. To substantiate this hypothesis, we examined whether CD9-positive cells isolated from IL-MCL of adult male rats differentiate into mesenchymal cells, such as endothelial cells, adipocytes, chondrocytes, and osteocytes. Immunohistochemical analysis revealed that the CD9-positive cells were positive for the MSC markers, CD349, CD105, CD271, and CD273 and were detected in the early postnatal period at the boundary between the posterior and intermediate lobes but not in the embryonic period. In addition, some adult tissue stem cells derived from external tissues were positive for both CD9 and MSC markers, indicating that few CD9/SOX2-positive cells in the IL-MCL of the pituitary gland are MSCs that invaded from external tissues during pituitary development in the early postnatal period and exist in the adult tissue stem cells as suppliers of hormone-producing and endothelial cells in the anterior lobe. These finding should have implications for application of CD9/SOX2-positive cells in regenerative therapy of the pituitary.</p>

The adenohypophysis is composed of the anterior and intermediate lobes (AL and IL, respectively), and secretes hormones that play an important role in reproduction. CD9- and SOX2-double (CD9/SOX2) positive cells located in the marginal cell layer (MCL) facing the Rathke's cleft in the AL and IL form the primary stem cell niche in the adult adenohypophysis of rats. In this study, we successfully obtained 3-dimensional (3D) cell aggregates that closely resembled the primary niche of MCL in vivo. After incubation in a Matrigel containing several growth factors, approximately 20% of the cells in the CD9/SOX2-positive cell aggregates were differentiated into hormone-producing cells. The cell aggregates generated in this study may provide insight into the regulation of the pituitary stem/progenitor cell niche and the turnover of hormone-producing cells.