We study an axion-like particle (ALP) that experiences a first-order phase transition with respect to its mass or potential minimum. This can be realized if the ALP obtains a potential from ...non-perturbative effects of SU(N) gauge theory that is confined via the first-order phase transition. Similar dynamics are achieved in the so-called trapped misalignment mechanism, where the ALP is trapped in a false vacuum at high temperatures until it begins to oscillate about the true minimum. The resulting ALP abundance is significantly enhanced compared to the standard misalignment mechanism, explaining dark matter in a broader parameter space that is accessible to experiments e.g. IAXO, ALPS-II, and DM-radio. Furthermore, the viable parameter space includes a region of the mass ma≃10−8−10−7eV and the ALP-photon coupling gaγγ≃10−11GeV−1 that can explain the recent observation of very high energy photons from GRB221009A via axion-photon oscillations. The parameter region suggests that the FOPT can generate gravitational waves that explain the NANOGrav hint. If the ALP in this region explains dark matter, then the ALP might have experienced a first-order phase transition. Finally we also discuss cosmological aspects of the dark sector that triggers the FOPT and propose a possible solution to the cooling problem of dark glueballs.
We explore a dynamical mechanism to realize the emergence of a global U(1)PQ symmetry and its spontaneous breaking at an intermediate scale for an axion solution to the strong CP problem. Such a ...dynamics is provided by a new supersymmetric QCD near the middle of conformal window that couples to fields spontaneously breaking the U(1)PQ symmetry. A large anomalous dimension of the U(1)PQ breaking fields leads to the suppression of explicit U(1)PQ-violating higher dimensional operators. The U(1)PQ breaking vacuum is generated at a scale hierarchically smaller than the Planck scale by a non-perturbative effect. The U(1)PQ breaking drives the conformal breaking, and all the new quarks become massive. The axion potential is generated by the ordinary color SU(3)C effect as the U(1)PQ symmetry is only anomalous under the SU(3)C. The saxion direction is stabilized by supersymmetry breaking and cosmologically harmless.
Astrocytes have been reported to exhibit neuroprotective action via various chemokines. Reports of the chemokine CCL6 in central nervous system cells show expression in cultured microglia, but many ...unexplained effects on neurons and astrocytes remain. In this study, cultured cerebral cortical neurons, astrocytes, and a mixed culture system were constructed, and expression levels of CCL6 and its effects on glutamate neurotoxicity were examined. When neuron cultures and neuron–astrocyte mixed cultures were treated with glutamate, neuronal cell death was observed in both, but was induced by lower concentrations of glutamate in monocultured neurons. In addition, pretreatment of neuron cultures with conditioned media from neuron–astrocyte mixed cultures inhibited glutamate neurotoxicity. CCL6 expression was not observed in fluorescence activated cell sorting analyses of neuron and astrocyte cultures, but was observed in astrocytes from cocultures of neurons and astrocytes. Higher CCL6 concentrations were found in media from cocultures of neurons and astrocytes than in culture media from neuron cultures. Pretreatment of neuron cell cultures with CCL6 for 24 h also protected against glutamate neurotoxicity. This protective effect was suppressed by an antagonist of the chemokine receptor CCR1. Furthermore, glutamate neurotoxicity in mixed neuron and astrocyte cultures was enhanced by pretreatments with the CCR1 antagonist. Finally, cotreatments with the phosphatidylinositol-3 kinase (PI3K) inhibitor and CCL6 abolished the neuroprotective effects of CCL6. These data suggest that astrocytes protect neurons by activating CCR1 in neurons. Moreover, this neuroprotective action of astrocyte CCL6 is mediated by CCR1, and downstream by PI3K.
•Pretreatment of neuron cell cultures with CCL6 protected against glutamate neurotoxicity via CCR1.•Astrocytes protect neurons by activating CCR1 in neurons.•This neuroprotective action of astrocyte CCL6 is mediated by CCR1, and downstream by PI3K.
Donepezil is a potent and selective acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease. In the present study, we investigated the responses of astrocytes to bradykinin, ...an inflammatory mediator, and the effect of donepezil on these responses using cultured cortical astrocytes. Bradykinin induced a transient increase of intracellular calcium concentration (Ca2+i) in cultured astrocytes. Bradykinin-induced Ca2+i increase was inhibited by the exposure to thapsigargin, which depletes Ca2+ stores on endoplasmic reticulum, but not by the exclusion of extracellular Ca2+. Twenty four hours pretreatment of donepezil reduced the bradykinin-induced Ca2+i increase. This reduction was inhibited not only by mecamylamine, a nAChR antagonist, but also by PI3K and Akt inhibitors. In addition, donepezil inhibited bradykinin-induced increase of the intracellular reactive oxygen species level in astrocytes. These results suggest that donepezil inhibits the inflammatory response induced by bradykinin via nAChR and PI3K-Akt pathway in astrocytes.
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