Myofiber necroptosis promotes muscle stem cell proliferation via releasing Tenascin-C during regeneration

Necroptosis, a form of programmed cell death, is characterized by the loss of membrane integrity and release of intracellular contents, the execution of which depends on the membrane-disrupting activity of the Mixed Lineage Kinase Domain-Like protein (MLKL) upon its phosphorylation. Here we found myofibers committed MLKL-dependent necroptosis after muscle injury. Either pharmacological inhibition of the necroptosis upstream kinase Receptor Interacting Protein Kinases 1 (RIPK1) or genetic ablation of MLKL expression in myofibers led to significant muscle regeneration defects. By releasing factors into the muscle stem cell (MuSC) microenvironment, necroptotic myofibers facilitated muscle regeneration. Tenascin-C (TNC), released by necroptotic myofibers, was found to be critical for MuSC proliferation. The temporary expression of TNC in myofibers is tightly controlled by necroptosis; the extracellular release of TNC depends on necroptotic membrane rupture. TNC directly activated EGF receptor (EGFR) signaling pathway in MuSCs through its N-terminus assembly domain together with the EGF-like domain. These findings indicate that necroptosis plays a key role in promoting MuSC proliferation to facilitate muscle regeneration.Subject terms: Necroptosis, Muscle stem cells     

Experimental vestibulopathy produced as a result of formation of a generator of pathologically enhanced excitation in the vestibular nuclei (phenomenon of a determinative dispatch station)]

A possibility of formation of a generator of pathologically enhanced excitation in the system of the vestibular nuclei of the medulla oblongata by disturbance of their inhibitory processes (resulting in development of contralateral rotatory motions in animals) was shown. Experiments with electrical stimulation of the lateral vestibular nucleus and its coagulation showed the system of the vestibular neurons organizing the synchronous message by the vestibulo-spinal pathways to underlie the generator of the pathologically enhanced excitation. It was concluded that the generator of the pathologically enhanced excitation formed in the lateral vestibular nucleus as a result of disturbed inhibition underlied the hyperactive determinative dispatch station causing the syndrome of vestibulopathy     

Cortical spreading depression aggravates early brain injury in a mouse model of subarachnoid hemorrhage

Cortical spreading depression (CSD) has been observed during the early phase of subarachnoid hemorrhage (SAH). However, the effect of CSD on the cerebral blood flow (CBF) and cerebral oxyhemoglobin (CHbO) during the early phase of SAH has not yet been assessed directly. We, therefore, used laser speckle imaging and optical intrinsic sinal imaging to record CBF and CHbO during CSD and cerebral cortex perfusion (CCP) at 24 hours after CSD in a mouse model of SAH. SAH was induced by blood injection into the prechiasmatic cistern. When CSD occurred, the change trend of CBF and CHbO in Sham group and SAH group was the same, but ischemia and hypoxia in SAH group was more significant. At 24 hours after SAH, the CCP of CSD group was lower than that of no CSD group, and the neurological function score of CSD group was lower. We conclude that induction of CSD further aggravates cerebral ischemia and worsens neurological dysfunction in the early stage of experimental SAH. Our study underscores the consequence of CSD in the development of early brain injury after SAH.     

Metabolism of prostaglandin endoperoxide by microsomes from cat lung

It has been reported that the prostaglandin (PG) precursor, arachidonic acid, produces divergent hemodynamic responses in the feline pulmonary vascular bed. However, the pattern of arachidonic acid products formed in the lung of this species is unknown. In order to determine the type and activity of terminal enzymes in the lung, prostaglandin biosynthesis by microsomes from cat lung was studied using the prostaglandin endoperoxide, PGH2, as a substrate. The major products of incubations of PGH2 with microsomes were thromboxane (TX) B2 (the major metabolite of TXA2), 6-keto-PGF1 alpha (the breakdown product of PGI2) and 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT). Formation of TXB2 was markedly reduced by imidazole. Tranylcypromine decreased the formation of TXB2 and HHT and inhibited the formation of 6-keto-PGF1 alpha. At low PGH2 concentrations, equal production of TXB2 and 6-keto-PGF1 alpha was observed. However, as PGH2 concentration increased, 6-keto-PGF1 alpha production approached early saturation while TXB2 production increased in a linear fashion. These results suggest that enzymatic formation of TXA2 and PGI2 is a function of substrate availability in the lung. These findings provide a possible explanation for the divergent hemodynamic responses to arachidonic acid infusions at high and low concentrations in the feline pulmonary vascular bed.     

Effect of adrenocorticotropin fragments on the memory of Tenebrio molitor beetles

Fragments of the adrenocorticotropic hormone ACTH1-24 and ACTH5-7 facilitate memory in the beetle T. molitor, the effect being observed at different stages after learning. An analogue of ACTH5-7 which contains D-phenylalamine, as well as D-phen7-ACTH4-7, inhibit memorization (the results checked 1 day after learning) and induce some other disturbances in the behaviour of beetles. To the 10th day of learning, the effects of the analogues cannot be distinguished from those of L-Phe7-fragments. The results obtained are compared with the known effect of ACTH fragments on memory in vertebrates.