Imbalance of p75(NTR)/TrkB protein expression in Huntington's disease: Implication for neuroprotective therapies

Neuroprotective therapies based on brain-derived neurotrophic factor (BDNF) administration have been proposed for Huntington's disease (HD) treatment. However, our group has recently reported reduced levels of TrkB in HD mouse models and HD human brain suggesting that besides a decrease on BDNF levels a reduction of TrkB expression could also contribute to diminished neurotrophic support in HD. BDNF can also bind to p75 neurotrophin receptor (p75(NTR)) modulating TrkB signaling. Therefore, in this study we have analyzed the levels of p75(NTR) in several HD models, as well as in HD human brain. Our data demonstrates a p75(NTR)/TrkB imbalance in the striatum of two different HD mouse models, Hdh(Q111/111) homozygous knockin mice and R6/1 mice that was also manifested in the putamen of HD patients. The imbalance between TrkB and p75(NTR) levels in a HD cellular model did not affect BDNF-mediated TrkB activation of prosurvival pathways but induced activation of apoptotic cascades as demonstrated by increased JNK phosphorylation. Moreover, BDNF failed to protect mutant huntingtin striatal cells transfected with p75(NTR) against NMDA-mediated excitotoxicity, which was associated with decreased Akt phosphorylation. Interestingly, lack of Akt activation following BDNF and NMDA treatment correlated with increased PP1 levels. Accordingly, pharmacological inhibition of PP1 by okadaic acid (OA) prevented mutant huntingtin striatal cell death induced by NMDA and BDNF. Altogether, our findings demonstrate that the p75(NTR)/TrkB imbalance induced by mutant huntingtin in striatal cells associated with the aberrant activity of PP1 disturbs BDNF neuroprotection likely contributing to increasing striatal vulnerability in HD. On the basis of this data we hypothesize that normalization of p75(NTR) and/or TrkB expression or their signaling will improve BDNF neuroprotective therapies in HD. Cell Death and Disease (2013) 4, e595; doi:10.1038/cddis.2013.116; published online 18 April 201

Quiet Sun magnetic fields from space-borne observations: simulating Hinode's case

We examine whether or not it is possible to derive the field strength distribution of quiet Sun internetwork regions from very high spatial resolution polarimetric observations in the visible. In particular, we consider the case of the spectropolarimeter attached to the Solar Optical Telescope aboard Hinode. Radiative magneto-convection simulations are used to synthesize the four Stokes profiles of the \ion{Fe}{1} 630.2 nm lines. Once the profiles are degraded to a spatial resolution of 0\farcs32 and added noise, we infer the atmospheric parameters by means of Milne-Eddington inversions. The comparison of the derived values with the real ones indicates that the visible lines yield correct internetwork field strengths and magnetic fluxes, with uncertainties smaller than $\sim$150 G, when a stray light contamination factor is included in the inversion. Contrary to the results of ground-based observations at 1\arcsec, weak fields are retrieved wherever the field is weak in the simulation.Comment: Accepted for publication in ApJ Letter

The formation and disintegration of magnetic bright points observed by Sunrise/IMaX

The evolution of the physical parameters of magnetic bright points (MBPs) located in the quiet Sun (mainly in the interwork) during their lifetime is studied. First we concentrate on the detailed description of the magnetic field evolution of three MBPs. This reveals that individual features follow different, generally complex, and rather dynamic scenarios of evolution. Next we apply statistical methods on roughly 200 observed MBP evolutionary tracks. MBPs are found to be formed by the strengthening of an equipartition field patch, which initially exhibits a moderate downflow. During the evolution, strong downdrafts with an average velocity of 2.4 km/s set in. These flows, taken together with the concurrent strengthening of the field, suggest that we are witnessing the occurrence of convective collapses in these features, although only 30% of them reach kG field strengths. This fraction might turn out to be larger when the new 4 m class solar telescopes are operational as observations of MBPs with current state of the art instrumentation could still be suffering from resolution limitations. Finally, when the bright point disappears (although the magnetic field often continues to exist) the magnetic field strength has dropped to the equipartition level and is generally somewhat weaker than at the beginning of the MBP's evolution. Noteworthy is that in about 10% of the cases we observe in the vicinity of the downflows small-scale strong (exceeding 2 km/s) intergranular upflows related spatially and temporally to these downflows.Comment: 19 pages, 13 figures; final version published in "The Astrophysical Journal

Applicability of Milne-Eddington inversions to high spatial resolution observations of the quiet Sun

The physical conditions of the solar photosphere change on very small spatial scales both horizontally and vertically. Such a complexity may pose a serious obstacle to the accurate determination of solar magnetic fields. We examine the applicability of Milne-Eddington (ME) inversions to high spatial resolution observations of the quiet Sun. Our aim is to understand the connection between the ME inferences and the actual stratifications of the atmospheric parameters. We use magnetoconvection simulations of the solar surface to synthesize asymmetric Stokes profiles such as those observed in the quiet Sun. We then invert the profiles with the ME approximation. We perform an empirical analysis of the heights of formation of ME measurements and analyze the uncertainties brought about by the ME approximation. We also investigate the quality of the fits and their relationship with the model stratifications. The atmospheric parameters derived from ME inversions of high-spatial resolution profiles are reasonably accurate and can be used for statistical analyses of solar magnetic fields, even if the fit is not always good. We also show that the ME inferences cannot be assigned to a specific atmospheric layer: different parameters sample different ranges of optical depths, and even the same parameter may trace different layers depending on the physical conditions of the atmosphere. Despite this variability, ME inversions tend to probe deeper layers in granules as compared with intergranular lanes.Comment: Accepted for publication in Astronomy and Astrophysic