Duloxetine by modulating the Akt/GSK3 signaling pathways has neuroprotective effects against methamphetamine-induced neurodegeneration and cognition impairment in rats

Background: The neuroprotective effects of duloxetine, as an antidepressant agent, and the neurodegenerative effects of methamphetamine have been shown in previous studies. Nonetheless, their exact neurochemical and behavioral effects are still unclear. In the current study, we sought to clarify the molecular mechanisms involved in the protective effects of duloxetine against methamphetamine-induced neurodegeneration. Methods: Forty adult male rats were divided randomly into 5 groups. Group 1 was the negative control and received normal saline, Group 2 was the positive control and received methamphetamine, and Groups 3, 4, and 5 were concurrently treated with methamphetamine (10 mg/kg) and duloxetine (5, 10, and 15 mg/kg, respectively). All the treatments were continued for 21 days. Between days 17 and 21, the Morris Water Maze (MWM) was used to assess learning and memory in the treated groups. On day 22, the hippocampus was isolated from each rat and oxidative, antioxidant, and inflammatory factors were measured. Additionally, the expression levels of the total and phosphorylated forms of the Akt and GSK3 proteins were evaluated via the ELISA method. Results: Duloxetine in all the administered doses ameliorated the effects of the methamphetamine-induced cognition impairment in the MWM. The chronic abuse of methamphetamine increased malondialdehyde, tumor necrosis factor-α, and interleukin-1β, while it decreased superoxide dismutase, glutathione peroxidase, and glutathione reductase activities. Duloxetine not only prevented these malicious effects of methamphetamine but also activated the expression of Akt (both forms) and inhibited the expression of GSK3 (both forms) in the methamphetamine-treated rats. Conclusion: We conclude that the Akt/GSK3 signaling pathways might have a critical role in the protective effects of duloxetine against methamphetamine-induced neurodegeneration and cognition impairment. © 2019, Shiraz University of Medical Sciences. All rights reserved

A Relativistic Mean Field Model for Entrainment in General Relativistic Superfluid Neutron Stars

General relativistic superfluid neutron stars have a significantly more intricate dynamics than their ordinary fluid counterparts. Superfluidity allows different superfluid (and superconducting) species of particles to have independent fluid flows, a consequence of which is that the fluid equations of motion contain as many fluid element velocities as superfluid species. Whenever the particles of one superfluid interact with those of another, the momentum of each superfluid will be a linear combination of both superfluid velocities. This leads to the so-called entrainment effect whereby the motion of one superfluid will induce a momentum in the other superfluid. We have constructed a fully relativistic model for entrainment between superfluid neutrons and superconducting protons using a relativistic $\sigma - \omega$ mean field model for the nucleons and their interactions. In this context there are two notions of ``relativistic'': relativistic motion of the individual nucleons with respect to a local region of the star (i.e. a fluid element containing, say, an Avogadro's number of particles), and the motion of fluid elements with respect to the rest of the star. While it is the case that the fluid elements will typically maintain average speeds at a fraction of that of light, the supranuclear densities in the core of a neutron star can make the nucleons themselves have quite high average speeds within each fluid element. The formalism is applied to the problem of slowly-rotating superfluid neutron star configurations, a distinguishing characteristic being that the neutrons can rotate at a rate different from that of the protons.Comment: 16 pages, 5 figures, submitted to PR

R-modes of neutron stars with the superfluid core

We investigate the modal properties of the $r$-modes of rotating neutron stars with the core filled with neutron and proton superfluids, taking account of entrainment effects between the superfluids. The stability of the $r$-modes against gravitational radiation reaction is also examined considering viscous dissipation due to shear and a damping mechanism called mutual friction between the superfluids in the core. We find the $r$-modes in the superfluid core are split into ordinary $r$-modes and superfluid $r$-modes, which we call, respectively, $r^o$- and $r^s$-modes. The two superfluids in the core flow together for the $r^o$-modes, while they counter-move for the $r^s$-modes. For the $r^o$-modes, the coefficient $\kappa_0\equiv\lim_{\Omega\to 0}\omega/\Omega$ is equal to $2m/[l^\prime(l^\prime+1)]$, almost independent of the parameter $\eta$ that parameterizes the entrainment effects between the superfluids, where $\Omega$ is the angular frequency of rotation, $\omega$ the oscillation frequency observed in the corotating frame of the star, and $l^\prime$ and $m$ are the indices of the spherical harmonic function representing the angular dependence of the $r$-modes. For the $r^s$-modes, on the other hand, $\kappa_0$ is equal to $2m/[l^\prime(l^\prime+1)]$ at $\eta=0$ (no entrainment), and it almost linearly increases as $\eta$ is increased from $\eta=0$. The mutual friction in the superfluid core is found ineffective to stabilize the $r$-mode instability caused by the $r^o$-mode except in a few narrow regions of $\eta$. The $r$-mode instability caused by the $r^s$-modes, on the other hand, is extremely weak and easily damped by dissipative processes in the star.Comment: 22 pages, 22 figures, accepted for publication in the Astrophysical Journa

Relativistic Two-stream Instability

We study the (local) propagation of plane waves in a relativistic, non-dissipative, two-fluid system, allowing for a relative velocity in the "background" configuration. The main aim is to analyze relativistic two-stream instability. This instability requires a relative flow -- either across an interface or when two or more fluids interpenetrate -- and can be triggered, for example, when one-dimensional plane-waves appear to be left-moving with respect to one fluid, but right-moving with respect to another. The dispersion relation of the two-fluid system is studied for different two-fluid equations of state: (i) the "free" (where there is no direct coupling between the fluid densities), (ii) coupled, and (iii) entrained (where the fluid momenta are linear combinations of the velocities) cases are considered in a frame-independent fashion (eg. no restriction to the rest-frame of either fluid). As a by-product of our analysis we determine the necessary conditions for a two-fluid system to be causal and absolutely stable and establish a new constraint on the entrainment.Comment: 15 pages, 2 eps-figure

Slowly Rotating General Relativistic Superfluid Neutron Stars with Relativistic Entrainment

Neutron stars that are cold enough should have two or more superfluids/supercondutors in their inner crusts and cores. The implication of superfluidity/superconductivity for equilibrium and dynamical neutron star states is that each individual particle species that forms a condensate must have its own, independent number density current and equation of motion that determines that current. An important consequence of the quasiparticle nature of each condensate is the so-called entrainment effect, i.e. the momentum of a condensate is a linear combination of its own current and those of the other condensates. We present here the first fully relativistic modelling of slowly rotating superfluid neutron stars with entrainment that is accurate to the second-order in the rotation rates. The stars consist of superfluid neutrons, superconducting protons, and a highly degenerate, relativistic gas of electrons. We use a relativistic $\sigma$ - $\omega$ mean field model for the equation of state of the matter and the entrainment. We determine the effect of a relative rotation between the neutrons and protons on a star's total mass, shape, and Kepler, mass-shedding limit.Comment: 30 pages, 10 figures, uses ReVTeX

R-Modes in Superfluid Neutron Stars

The analogs of r-modes in superfluid neutron stars are studied here. These modes, which are governed primarily by the Coriolis force, are identical to their ordinary-fluid counterparts at the lowest order in the small angular-velocity expansion used here. The equations that determine the next order terms are derived and solved numerically for fairly realistic superfluid neutron-star models. The damping of these modes by superfluid ``mutual friction'' (which vanishes at the lowest order in this expansion) is found to have a characteristic time-scale of about 10^4 s for the m=2 r-mode in a ``typical'' superfluid neutron-star model. This time-scale is far too long to allow mutual friction to suppress the recently discovered gravitational radiation driven instability in the r-modes. However, the strength of the mutual friction damping depends very sensitively on the details of the neutron-star core superfluid. A small fraction of the presently acceptable range of superfluid models have characteristic mutual friction damping times that are short enough (i.e. shorter than about 5 s) to suppress the gravitational radiation driven instability completely.Comment: 15 pages, 8 figure

r-modes in Relativistic Superfluid Stars

We discuss the modal properties of the $r$-modes of relativistic superfluid neutron stars, taking account of the entrainment effects between superfluids. In this paper, the neutron stars are assumed to be filled with neutron and proton superfluids and the strength of the entrainment effects between the superfluids are represented by a single parameter $\eta$. We find that the basic properties of the $r$-modes in a relativistic superfluid star are very similar to those found for a Newtonian superfluid star. The $r$-modes of a relativistic superfluid star are split into two families, ordinary fluid-like $r$-modes ($r^o$-mode) and superfluid-like $r$-modes ($r^s$-mode). The two superfluids counter-move for the $r^s$-modes, while they co-move for the $r^o$-modes. For the $r^o$-modes, the quantity $\kappa\equiv\sigma/\Omega+m$ is almost independent of the entrainment parameter $\eta$, where $m$ and $\sigma$ are the azimuthal wave number and the oscillation frequency observed by an inertial observer at spatial infinity, respectively. For the $r^s$-modes, on the other hand, $\kappa$ almost linearly increases with increasing $\eta$. It is also found that the radiation driven instability due to the $r^s$-modes is much weaker than that of the $r^o$-modes because the matter current associated with the axial parity perturbations almost completely vanishes.Comment: 14 pages, 4 figures. To appear in Physical Review

Nonextensive thermal sources of cosmic rays?

The energy spectrum of cosmic rays (CR) exhibits power-like behavior with a very characteristic "knee" structure. We consider a possibility that such a spectrum could be generated by some specific nonstatistical temperature fluctuations in the source of CR with the "knee" structure reflecting an abrupt change of the pattern of such fluctuations. This would result in a generalized nonextensive statistical model for the production of CR. The possible physical mechanisms leading to these effects are discussed together with the resulting chemical composition of the CR, which follows the experimentally observed abundance of nuclei.Comment: 16 pages, 3 figures, rewritten and updated version, to be published in Centr. Eur. J. Phy