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Microglial research has advanced considerably in recent decades yet has been constrained by a rolling series of dichotomies such as "resting versus activated" and "M1 versus M2." This dualistic classification of good or bad microglia is inconsistent with the wide repertoire of microglial states and functions in development, plasticity, aging, and diseases that were elucidated in recent years. New designations continuously arising in an attempt to describe the different microglial states, notably defined using transcriptomics and proteomics, may easily lead to a misleading, although unintentional, coupling of categories and functions. To address these issues, we assembled a group of multidisciplinary experts to discuss our current understanding of microglial states as a dynamic concept and the importance of addressing microglial function. Here, we provide a conceptual framework and recommendations on the use of microglial nomenclature for researchers, reviewers, and editors, which will serve as the foundations for a future white paper.

Molecular hydrogen (H2) has antioxidant, anti-inflammatory, and anti-fibrotic effects. In a rat model simulating pulmonary fibrotic changes induced by monocrotaline-induced pulmonary hypertension (MPH), we had previously explored the impact of inhaled H2 on lung inflammation and blood pressure. In this study, we further focused the biological effects of H2 on mast cells (MCs) and the parameters of the fibrotic phenotype of the local tissue microenvironment. MPH resulted in a significantly increased number of MCs in both the pneumatic and respiratory parts of the lungs, an increased number of tryptase-positive MCs with increased expression of TGF-β, activated interaction with immunocompetent cells (macrophages and plasma cells) and fibroblasts, and increased MC colocalization with a fibrous component of the extracellular matrix of connective tissue. The alteration in the properties of the MC population occurred together with intensified collagen fibrillogenesis and an increase in the integral volume of collagen and elastic fibers of the extracellular matrix of the pulmonary connective tissue. The exposure of H2 together with monocrotaline (MCT), despite individual differences between animals, tended to decrease the intrapulmonary MC population and the severity of the fibrotic phenotype of the local tissue microenvironment compared to changes in animals exposed to the MCT effect alone. In addition, the activity of collagen fibrillogenesis associated with MCs and the expression of TGF-β and tryptase in MCs decreased, accompanied by a reduction in the absolute and relative content of reticular and elastic fibers in the lung stroma. Thus, with MCT exposure, inhaled H2 has antifibrotic effects involving MCs in the lungs of rats. This reveals the unknown development mechanisms of the biological effects of H2 on the remodeling features of the extracellular matrix under inflammatory background conditions of the tissue microenvironment. [ABSTRACT FROM AUTHOR]

Sleep deprivation (SD) triggers mitochondrial dysfunction and neural inflammation, leading to cognitive impairment and mental issues. However, the mechanism involving mitochondrial dysfunction and neural inflammation still remains unclear. Here, we report that SD rats exhibited multiple behavioral disorders, brain oxidative stress, and robust brain mitochondrial DNA (mtDNA) oxidation. In particular, SD activated microglia and microglial mtDNA efflux to the cytosol and provoked brain pro-inflammatory cytokines. We observed that the mtDNA efflux and pro-inflammatory cytokines significantly reduced with the suppression of the mtDNA oxidation. With the treatment of a novel mitochondrial nutrient, hydroxytyrosol butyrate (HTHB), the SD-induced behavioral disorders were significantly ameliorated while mtDNA oxidation, mtDNA release, and NF-κB activation were remarkably alleviated in both the rat brain and the N9 microglial cell line. Together, these results indicate that microglial mtDNA oxidation and the resultant release induced by SD mediate neural inflammation and HTHB prevents mtDNA oxidation and efflux, providing a potential treatment for SD-induced mental issues. [ABSTRACT FROM AUTHOR]

Molecular hydrogen ([H.sub.2]) showed protection against various kinds of oxidative-stress-related diseases. First, it was reported that the mechanism of therapeutic effects of [H.sub.2] was antioxidative effect due to inhibition of the most cytotoxic reactive oxygen species, hydroxy radical (*OH). However, after chronic administration of [H.sub.2] in drinking water, oxidative-stress-induced nerve injury is significantly attenuated even in the absence of [H.sub.2]. It suggests indirect signaling of [H.sub.2] and gastrointestinal tract is involved. Indirect effects of [H.sub.2] could be tested by giving [H.sub.2] water only before nerve injury, as preconditioning. For example, preconditioning of [H.sub.2] for certain a period (~7 days) in Parkinson's disease model mice shows significant neuroprotection. As the mechanism of indirect effect, [H.sub.2] in drinking water induces ghrelin production and release from the stomach via [beta]1-adrenergic receptor stimulation. Released ghrelin circulates in the body, being transported across the blood-brain barrier, activates its receptor, growth-hormone secretagogue receptor. [H.sub.2]-induced upregulation of ghrelin mRNA is also shown in ghrelin-producing cell line, SG-1. These observations help with understanding the chronic effects of [H.sub.2] and raise intriguing preventive and therapeutic options using [H.sub.2]. Key words: molecular hydrogen, preconditioning, Parkinson's disease, ghrelin. L'hydrogene moleculaire ([H.sub.2]) est decrit comme etant protecteur contre divers types de maladies liees au stress oxydatif. Il a d'abord ete rapporte que le mode d'action des effets therapeutiques de l'[H.sub.2] etait un effet antioxydant cause par l'inhibition du radical hydroxyl (*OH), le derive reactif de l'oxygene le plus toxique. Cependant, apres l'administration a long terme d'[H.sub.2] dans l'eau a boire, les lesions nerveuses provoquees parle stress oxydatif sont nettement attenuees, meme en absence d'[H.sub.2]. Cela laisse entendre qu'il existerait une voie de signalisation indirecte de l'[H.sub.2] et que le tractus gastro-intestinal jouerait un role. Les effets indirects de l'[H.sub.2] pourraient etre evalues en donnant de l'eau avec [H.sub.2] seulement, avant les lesions nerveuses, en tant que preconditionnement. Par exemple, le preconditionnement par l'[H.sub.2] pendant une certaine periode (~7 jours) dans un modele murin de maladie de Parkinson permet d'obtenir une neuroprotection notable. Comme mode d'action d'un effet indirect, l'[H.sub.2] dans l'eau a boire engendre la production et la liberation de ghreline par l'estomac par l'intermediaire d'une stimulation des recepteurs [beta]1-adrenergiques. La ghreline liberee circule dans l'organisme, transportee a travers la barriere hemo-encephalique, active son recepteur secretagogue d'hormone de croissance (GHSR). Nous observons aussi la regulation a la hausse de l'ARNm de ghreline engendre par l'[H.sub.2] dans des lignees cellulaires productrices de ghreline (SG- 1). Ces observations contribuent a la comprehension des effets a long terme de l'[H.sub.2] et laissent entrevoir d'interessantes options therapeutiques et de prevention fondees sur l'utilisation de l'[H.sub.2]. [Traduit par la Redaction] Mots-cles : hydrogene moleculaire, preconditionnement, maladie de Parkinson, ghreline., Introduction Inhaling molecular hydrogen ([H.sub.2]) showed protection against brain injury induced by focal ischemia and reperfusion in rat by reducing hydroxy radical (*OH), the most toxic reactive oxygen species (Ohsawa [...]

The article Nicotine inhibits activation of microglial proton currents via interactions with [alpha]7 acetylcholine receptors, written by Mami Noda and AI Kobayashi, was originally published Online First without open access. After publication in volume 67, issue 1, pages 235-245, Author(s): Mami Noda[sup.1] and AI Kobayashi[sup.1] Correction to: J Physiol Sci (2017) 67:235-245 https://doi.org/10.1007/s12576-016-0460-5 The article Nicotine inhibits activation of microglial proton currents via interactions with [alpha]7 acetylcholine receptors, written [...]