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The homeostatic regulation of sleep is characterized by rebound sleep after prolonged wakefulness, but the molecular and cellular mechanisms underlying this regulation are still unknown. In this study, we show that Ca2+/calmodulin-dependent protein kinase II (CaMKII)-dependent activity control of parvalbumin (PV)-expressing cortical neurons is involved in homeostatic regulation of sleep in male mice. Prolonged wakefulness enhances cortical PV-neuron activity. Chemogenetic suppression or activation of cortical PV neurons inhibits or induces rebound sleep, implying that rebound sleep is dependent on increased activity of cortical PV neurons. Furthermore, we discovered that CaMKII kinase activity boosts the activity of cortical PV neurons, and that kinase activity is important for homeostatic sleep rebound. Here, we propose that CaMKII-dependent PV-neuron activity represents negative feedback inhibition of cortical neural excitability, which serves as the distributive cortical circuits for sleep homeostatic regulation. The role of cortical PV neurons in the regulation of sleep architecture and homeostatic sleep rebound is not fully understood. Here, the authors show that CaMKII-mediated control of cortical parvalbumin-neuron activity regulates the homeostatic sleep rebound in mice. [ABSTRACT FROM AUTHOR]

The Dja2 knockout (Dja2−/−) mice had respiratory distress, and >60% died within 2 days after birth. The surviving adult Dja2−/− mice were infertile and the lungs of Dja2−/− mice showed several abnormalities, including the processing defect of prosurfactant protein C in the alveolar epithelial type II cells and the accumulation of glycolipids in enlarged alveolar macrophages. The luminal pH of acidic organelles in Dja2−/− cells was shifted to pH 5.37–5.45. This deviated pH was immediately restored to control levels (pH 4.56–4.65) by the addition of a diuretic, ethyl isopropyl amiloride (EIPA). Although the role of DJA2 in maintaining the pH homeostasis of lysosome‐related organelles is currently obscure, this rapid and remarkable pH resilience is best explained by an EIPA‐sensitive proton efflux machinery that is disorganized and overactivated due to the loss of Dja2. [ABSTRACT FROM AUTHOR]

Introduction: In many mammals, the testes descend from its abdominal position on the mesonephric kidney, and are housed in the scrotum. It has been speculated that metatherians and eutherians might have acquired the scrotal testis independently, because metatherians have the scrotum cranially to the phallus, while eutherians, such as humans and mice, possess it caudally. Rather, recent studies, based on sequence comparisons of testis-descent-related genes indicate that the metatherian-eutherian common ancestor might already possess the descent mechanisms. To further elucidate the path of scrotal testis evolution, it is informative to compare the processes of the descent and scrotum development between metatherian and eutherian model animals., Methods: In this study, we histologically and molecularly compare these processes in gray short-tailed opossum (Monodelphis domestica), the most commonly used metatherian experimental model, and compare them with those in mouse., Results: Our observations indicate that, while trans-abdominal phase of the descent appears to be largely similar, scrotal phase differs, due to their distinct scrotum positions. Our cell-labeling analyses and dynamic expression of Gsc1 reveal extensive cell/tissue rearrangements in murine scrotal development. In contrast, Gsc1 is not expressed in the developing genitalia and scrotal primordium of the opossum., Conclusion: Our results suggest recruitment of new regulatory pathways for the scrotum development and the scrotal phase of the testis descent during the evolution of eutherian mammals., (The Author(s). Published by S. Karger AG, Basel.)