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Vasopressin secretion from the magnocellular neurosecretory cells (MNCs) is crucial for body fluid homeostasis. Osmotic regulation of MNC activity involves the concerted modulation of intrinsic mechanosensitive ion channels, taurine release from local astrocytes as well as excitatory inputs derived from osmosensitive forebrain regions. Extracellular signal-regulated protein kinases (ERK) are mitogen-activated protein kinases that transduce extracellular stimuli into intracellular post-translational and transcriptional responses, leading to changes in intrinsic neuronal properties and synaptic function. Here, we investigated whether ERK activation (i.e. phosphorylation) plays a role in the functioning of forebrain osmoregulatory networks. We found that within 10 min after intraperitoneal injections of hypertonic saline (3 m, 6 m) in rats, many phosphoERK-immunopositive neurones were observed in osmosensitive forebrain regions, including the MNC containing supraoptic nuclei. The intensity of ERK labelling was dose-dependent. Reciprocally, slow intragastric infusions of water that lower osmolality reduced basal ERK phosphorylation. In the supraoptic nucleus, ERK phosphorylation predominated in vasopressin neurones vs. oxytocin neurones and was absent from astrocytes. Western blot experiments confirmed that phosphoERK expression in the supraoptic nucleus was dose dependent. Intracerebroventricular administration of the ERK phosphorylation inhibitor U 0126 before a hyperosmotic challenge reduced the number of both phosphoERK-immunopositive neurones and Fos expressing neurones in osmosensitive forebrain regions. Blockade of ERK phosphorylation also reduced hypertonically induced depolarization and an increase in firing of the supraoptic MNCs recorded in vitro. It finally reduced hypertonically induced vasopressin release in the bloodstream. Altogether, these findings identify ERK phosphorylation as a new element contributing to the osmoregulatory mechanisms of vasopressin release.
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http://dx.doi.org/10.1113/jphysiol.2013.261008 | DOI Listing |
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View Article and Find Full Text PDFTransl Psychiatry
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This study establishes mirdametinib as the first MEK inhibitor that can undergo clinical development for psychiatric indications such as post-traumatic stress disorder (PTSD). PTSD is characterized by persistent traumatic memories with limited effective treatment options. A body of evidence suggests that memory storage is dynamic and constantly updated through post-retrieval modification a process termed reconsolidation.
View Article and Find Full Text PDFJ Dairy Sci
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Dairy Nutrition and Function, Key Laboratory of Sichuan Province, New Hope Dairy Co., Ltd., Chengdu, Sichuan, 610023, China; Chengdu Molecular Power Biotechnology Co., Ltd., Chengdu, Sichuan, 611732; China.
Sarcopenia is an age-related muscle loss, fiber number and decreased regenerative capacity with increased abundance of ROS levels and electron transport chain (ETC) abnormalities. The aim of the study is to investigate the anti-sarcopenia effect of MFG-E8 in alleviating skeletal muscle dysfunction induced by D-gal, reveal the mechanism on promoting myoblast cell proliferation and mediating cell cycle. In vivo experiment showed that MFG-E8 can improve the anti-oxidant status and increase soleus muscle mass (35.
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