Does neuroinflammation turn on the flame in Alzheimer's disease? Focus on astrocytes

Data from animal models and Alzheimer's disease (AD) subjects provide clear evidence for an activation of inflammatory pathways during the pathogenetic course of such illness. Biochemical and neuropathological studies highlighted an important cause/effect relationship between inflammation and AD progression, revealing a wide range of genetic, cellular, and molecular changes associated with the pathology. In this context, glial cells have been proved to exert a crucial role. These cells, in fact, undergo important morphological and functional changes and are now considered to be involved in the onset and progression of AD. In particular, astrocytes respond quickly to pathology with changes that have been increasingly recognized as a continuum, with potentially beneficial and/or negative consequences. Although it is now clear that activated astrocytes trigger the neuroinflammatory process, however, the precise mechanisms have not been completely elucidated. Neuroinflammation is certainly a multi-faceted and complex phenomenon and, especially in the early stages, exerts a reparative intent. However, for reasons not yet all well known, this process goes beyond the physiologic control and contributes to the exacerbation of the damage. Here we scrutinize some evidence supporting the role of astrocytes in the neuroinflammatory process and the possibility that these cells could be considered a promising target for future AD therapies

Magnetar-like activity from the central compact object in the SNR RCW103

The 6.67 hr periodicity and the variable X-ray flux of the central compact object (CCO) at the center of the SNR RCW 103, named 1E 161348-5055, have been always difficult to interpret within the standard scenarios of an isolated neutron star or a binary system. On 2016 June 22, the Burst Alert Telescope (BAT) onboard Swift detected a magnetar-like short X-ray burst from the direction of 1E 161348-5055, also coincident with a large long-term X-ray outburst. Here we report on Chandra, NuSTAR, and Swift (BAT and XRT) observations of this peculiar source during its 2016 outburst peak. In particular, we study the properties of this magnetar-like burst, we discover a hard X-ray tail in the CCO spectrum during outburst, and we study its long-term outburst history (from 1999 to July 2016). We find the emission properties of 1E 161348-5055 consistent with it being a magnetar. However in this scenario, the 6.67 hr periodicity can only be interpreted as the rotation period of this strongly magnetized neutron star, which therefore represents the slowest pulsar ever detected, by orders of magnitude. We briefly discuss the viable slow-down scenarios, favoring a picture involving a period of fall-back accretion after the supernova explosion, similarly to what is invoked (although in a different regime) to explain the "anti-magnetar" scenario for other CCOs.Comment: 6 pages, 3 figures. To be published in the Astrophysical Journal Letters; replaced to match the version accepted for publication on 2016 August 1

The first deep X-ray and optical observations of the closest isolated radio pulsar

With a distance of 170 pc, PSR J2144-3933 is the closest isolated radio pulsar currently known. It is also the slowest and least energetic radio pulsar; indeed, its radio emission is difficult to account for with standard pulsar models, since its position in the P-Pdot diagram is far beyond typical "death lines". Here we present the first deep X-ray and optical observations of PSR J2144-3933, performed in 2009 with XMM-Newton and the VLT, from which we can set one of the most robust upper limits on the surface temperature of a neutron star. We have also explored the possibility of measuring the neutron star mass from the gravitational lensing effect on a background optical source.Comment: 4 pages, 3 figures; to appear in the Proceedings of the Pulsar Conference 2010, Chia, Sardinia (Italy), 10-15 October 201

S100B inhibitor pentamidine attenuates reactive gliosis and reduces neuronal loss in a mouse model of Alzheimer's disease

Among the different signaling molecules released during reactive gliosis occurring in Alzheimer’s disease (AD), the astrocytederived S100B protein plays a key role in neuroinflammation, one of the hallmarks of the disease. The use of pharmacological tools targeting S100B may be crucial to embank its effects and some of the pathological features of AD. The antiprotozoal drug pentamidine is a good candidate since it directly blocks S100B activity by inhibiting its interaction with the tumor suppressor p53. We used a mouse model of amyloid beta- (A-) induced AD, which is characterized by reactive gliosis and neuroinflammation in the brain, and we evaluated the effect of pentamidine on the main S100B-mediated events. Pentamidine caused the reduction of glial fibrillary acidic protein, S100B, and RAGE protein expression, which are signs of reactive gliosis, and induced p53 expression in astrocytes. Pentamidine also reduced the expression of proinflammatory mediators and markers, thus reducing neuroinflammation in AD brain. In parallel, we observed a significant neuroprotection exerted by pentamidine on CA1 pyramidal neurons. We demonstrated that pentamidine inhibits A-induced gliosis and neuroinflammation in an animal model of AD, thus playing a role in slowing down the course of the disease

On the asymptotic behavior of the eigenvalues of nonlinear elliptic problems in domains becoming unbounded

We analyze the asymptotic behavior of the eigenvalues of nonlinear elliptic problems under Dirichlet boundary conditions and mixed (Dirichlet, Neumann) boundary conditions on domains becoming unbounded. We make intensive use of Picone identity to overcome nonlinearity complications. Altogether the use of Picone identity makes the proof easier with respect to the known proof in the linear case. Surprisingly the asymptotic behavior under mixed boundary conditions critically differs from the case of pure Dirichlet boundary conditions for some class of problems.Comment: 15 page

Discovery of spin-up in the X-ray pulsar companion of the hot subdwarf HD 49798

The hot subdwarf HD 49798 has an X-ray emitting compact companion with a spin-period of 13.2 s and a dynamically measured mass of 1.28+/-0.05 M_sun, consistent with either a neutron star or a white dwarf. Using all the available XMM-Newton and Swift observations of this source, we could perform a phase-connected timing analysis extending back to the ROSAT data obtained in 1992. We found that the pulsar is spinning up at a rate of (2.15+/-0.05)x10^{-15} s/s. This result is best interpreted in terms of a neutron star accreting from the wind of its subdwarf companion, although the remarkably steady period derivative over more than 20 years is unusual in wind-accreting neutron stars. The possibility that the compact object is a massive white dwarf accreting through a disk cannot be excluded, but it requires a larger distance and/or properties of the stellar wind of HD 49798 different from those derived from the modelling of its optical/UV spectra.Comment: Accepted for publication in MNRA