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Background: Thyrotropin-releasing hormone (TRH) was the first hypothalamic hormone isolated that stimulates pituitary thyrotropin (TSH) secretion. TRH was also later found to be a stimulator of pituitary prolactin and distributed throughout the brain, gastrointestinal tract, and pancreatic β cells. We previously reported the development of TRH null mice (conventional TRHKO), which exhibit characteristic tertiary hypothyroidism and impaired glucose tolerance due to insufficient insulin secretion. Although in the past five decades many investigators, us included, have attempted to determine the hypothalamic nucleus responsible for the hypothalamic–pituitary–thyroid (HPT) axis, it remained obscure because of the broad expression of TRH. Methods: To determine the hypothalamic region functionally responsible for the HPT axis, we established paraventricular nucleus (PVN)-specific TRH knockout (PVN-TRHKO) mice by mating Trh floxed mice and single-minded homolog 1 (Sim1)-Cre transgenic mice. We originally confirmed that most Sim1 was expressed in the PVN using Sim1-Cre/tdTomato mice. Results: These PVN-TRHKO mice exhibited tertiary hypothyroidism similar to conventional TRHKO mice; however, they did not show the impaired glucose tolerance observed in the latter, suggesting that TRH from non-PVN sources is essential for glucose regulation. In addition, a severe reduction in prolactin expression was observed in the pituitary of PVN-TRHKO mice compared with that in TRHKO mice. Conclusions: These findings are conclusive evidence that the PVN is the center of the HPT axis for regulation of serum levels of thyroid hormones and that the serum TSH levels are not decreased in tertiary hypothyroidism. We also noted that TRH from the PVN regulated prolactin, whereas TRH from non-PVN sources regulated glucose metabolism. [ABSTRACT FROM AUTHOR]

At the 93rd annual meeting of the Physiological Society of Japan, a symposium entitled 'Expanding frontiers in weight-control research explored by young investigators' was organized. The latest research on weight control was presented by young up-and-coming investigators. The symposium consisted of the following presentations: Gastrointestinal brush cells, immunity, and energy homeostasis; Impact of a brown rice-derived bioactive product on feeding regulation and fuel metabolism; A novel G protein-coupled receptor-regulated neuronal signaling pathway triggers sustained orexigenic effects; and NMDA receptor co-agonist d-serine regulates food preference. These four talks presented at the symposium were summarized as a series of short reviews in this review. Keywords: Type 2 immune response, [gamma]-Oryzanol, Appetite, DREADD, Anorexia, Author(s): Yoshiro Ishimaru[sup.1], Chisayo Kozuka[sup.2], Kenichiro Nakajima[sup.1] and Tsutomu Sasaki[sup.3] Main text Gastrointestinal brush cells, immunity, and energy homeostasis (by Yoshiro Ishimaru) The intestinal epithelium has at least two critical [...]

Palladium(II) and platinum(II) complexes with 1,4,8,11-tetramethyl-1,4,8,11-tetraphosphacyclotetradecane were produced by a template reaction. The bromide salts of the Pd2+ and Pt2+ complexes were isolated and their molecular structures were determined by X-ray crystallography. Both compounds were observed to have a square-planar geometry with a trans III(RRSS) configuration for the four asymmetric phosphorus atoms.

Early reperfusion after endovascular thrombectomy is associated with an improved outcome in ischemic stroke patients; however, the time dependency in elderly patients remains unclear. We investigated the time–outcome relationships in different age subgroups. Of 2420 patients enrolled in the RESCUE-Japan Registry 2 study, a study based on a prospective registry of stroke patients with acute cerebral large-vessel occlusion at 46 centers, we analyzed the data of 1010 patients with successful reperfusion after endovascular therapy (mTICI of 2b or 3). In 3 age subgroups (< 70, 70 to < 80, and ≥ 80 years), the mRS scores at 90 days were analyzed according to 4 categories of onset-to-reperfusion time (< 180, 180 to < 240, 240 to < 300, and ≥ 300 min). In each age subgroup, the distributions of mRS scores were better with shorter onset-to-reperfusion times. The adjusted common odds ratios for better outcomes per 1-category delay in onset-to-reperfusion time were 0.66 (95% CI 0.55–0.80) in ages < 70 years, 0.66 (95% CI 0.56–0.79) in ages 70 to < 80 years, and 0.83 (95% CI 0.70–0.98) in ages ≥ 80 years. Early reperfusion was associated with better outcomes across all age subgroups. Achieving early successful reperfusion is important even in elderly patients. [ABSTRACT FROM AUTHOR]

Abstract Background The intracellular deposition of misfolded proteins is a common neuropathological hallmark of most neurodegenerative disorders. Increasing evidence suggests that these pathogenic proteins may spread to neighboring cells and induce the propagation of neurodegeneration. Results In this study, we have demonstrated that α-synuclein (αSYN), a major constituent of intracellular inclusions in synucleinopathies, was taken up by neuronal and oligodendroglial cells in both a time- and concentration-dependent manner. Once incorporated, the extracellular αSYN was immediately assembled into high-molecular-weight oligomers and subsequently formed cytoplasmic inclusion bodies. Furthermore, αSYN uptake by neurons and cells of the oligodendroglial lineage was markedly decreased by the genetic suppression and pharmacological inhibition of the dynamin GTPases, suggesting the involvement of the endocytic pathway in this process. Conclusions Our findings shed light on the mode of αSYN uptake by neuronal and oligodendroglial cells and identify therapeutic strategies aimed at reducing the propagation of protein misfolding.