GABAB receptors-mediated tonic inhibition of glutamate release from A\u3b2 fibers in rat laminae III/IV of the spinal cord dorsal horn.

Presynaptic GABAB receptors (GABABRs) are highly expressed in dorsal root ganglion neurons and spinal cord dorsal horn. GABABRs located in superficial dorsal horn play an important antinociceptive role, by acting at both pre- and postsynaptic sites. GABABRs expressed in deep dorsal horn could be involved in the processing of touch sensation and possibly in the generation of tactile allodynia in chronic pain. The objective of this study was to characterize the morphological and functional properties of GABABRs expressed on A\u3b2 fibers projecting to lamina III/IV and to understand their role in modulating excitatory synaptic transmission. We performed high-resolution electron microscopic analysis, showing that GABAB2 subunit is expressed on 71.9% of terminals in rat lamina III-IV. These terminals were engaged in axodendritic synapses and, for the 46%, also expressed glutamate immunoreactivity. Monosynaptic excitatory postsynaptic currents, evoked by A\u3b2 fiber stimulation and recorded from lamina III/IV neurons in spinal cord slices, were strongly depressed by application of baclofen (0.1-2.5\u2009\ub5M), acting as a presynaptic modulator. Application of the GABABR antagonist CGP 55845 caused, in a subpopulation of neurons, the potentiation of the first of two excitatory postsynaptic currents recorded with the paired-pulse protocol, showing that GABABRs are endogenously activated. A decrease in the paired-pulse ratio accompanied the effect of CGP 55845, implying the involvement of presynaptic GABABRs. CGP 55845 facilitated only the first excitatory postsynaptic current also during a train of four consecutive stimuli applied to A\u3b2 fibers. These results suggest that GABABRs tonically inhibit glutamate release from A\u3b2 fibers at a subset of synapses in deep dorsal horn. This modulation specifically affects only the early phase of synaptic excitation in lamina III-IV neuron

Association of caspase 3 activation and h2ax γ phosphorylation in the aging brain: Studies on untreated and irradiated mice

Phosphorylation of H2AX is a response to DNA damage, but γH2AX also associates with mitosis and/or apoptosis. We examined the effects of X-rays on DNA integrity to shed more light on the significance of H2AX phosphorylation and its relationship with activation of caspase 3 (CASP3), the main apoptotic effector. After administration of the S phase marker BrdU, brains were collected from untreated and irradiated (10 Gray) 24-month-old mice surviving 15 or 30 min after irradiation. After paraffin embedding, brain sections were single- or double-stained with antibodies against γH2AX, p53-binding protein 1 (53BP1) (which is recruited during the DNA damage response (DDR)), active CASP3 (cCASP3), 5-Bromo-2-deoxyuridine (BrdU), and phosphorylated histone H3 (pHH3) (which labels proliferating cells). After statistical analysis, we demonstrated that irradiation not only induced a robust DDR with the appearance of γH2AX and upregulation of 53BP1 but also that cells with damaged DNA attempted to synthesize new genetic material from the rise in BrdU immunostaining, with increased expression of cCASP3. Association of γH2AX, 53BP1, and cCASP3 was also evident in normal nonirradiated mice, where DNA synthesis appeared to be linked to disturbances in DNA repair mechanisms rather than true mitotic activity

Protective effects of some grapevine polyphenols against naturally occurring neuronal death

The interest in the biological properties of grapevine polyphenols (PPs) in neuroprotection is continuously growing in the hope of finding translational applications. However, there are several concerns about the specificity of action of these molecules that appear to act non-specifically on the permeability of cellular membranes. Naturally occurring neuronal death (NOND) during cerebellar maturation is a well characterized postnatal event that is very useful to investigate the death and rescue of neurons. We here aimed to establish a baseline comparative study of the potential to counteract NOND of certain grapevine PPs of interest for the oenology. To do so, we tested ex vivo the neuroprotective activity of peonidin- and malvidin-3-O-glucosides, resveratrol, polydatin, quercetin-3-O-glucoside, (+)-taxifolin, and (+)-catechin. The addition of these molecules (50 μM) to organotypic cultures of mouse cerebellum explanted at postnatal day 7, when NOND reaches a physiological peak, resulted in statistically significant (two-tailed Mann–Whitney test—p < 0.001) reductions of the density of dead cells (propidium iodide+ cells/mm2) except for malvidin-3-O-glucoside. The stilbenes were less effective in reducing cell death (to 51–60%) in comparison to flavanols, (+)-taxifolin and quercetin 3-O-glucoside (to 69–72%). Thus, molecules with a -OH group in ortho position (taxifolin, quercetin 3-O-glucoside, (+)-catechin, and peonidin 3-O-glucoside) have a higher capability to limit death of cerebellar neurons. As NOND is apoptotic, we speculate that PPs act by inhibiting executioner caspase 3

Ghrelin in Central Neurons

Ghrelin, an orexigenic peptide synthesized by endocrine cells of the gastric mucosa, is released in the bloodstream in response to a negative energetic status. Since discovery, the hypothalamus was identified as the main source of ghrelin in the CNS, and effects of the peptide have been mainly observed in this area of the brain. In recent years, an increasing number of studies have reported ghrelin synthesis and effects in specific populations of neurons also outside the hypothalamus. Thus, ghrelin activity has been described in midbrain, hindbrain, hippocampus, and spinal cord. The spectrum of functions and biological effects produced by the peptide on central neurons is remarkably wide and complex. It ranges from modulation of membrane excitability, to control of neurotransmitter release, neuronal gene expression, and neuronal survival and proliferation. There is not at present a general consensus concerning the source of ghrelin acting on central neurons. Whereas it is widely accepted that the hypothalamus represents the most important endogenous source of the hormone in CNS, the existence of extra-hypothalamic ghrelin-synthesizing neurons is still controversial. In addition, circulating ghrelin can theoretically be another natural ligand for central ghrelin receptors. This paper gives an overview on the distribution of ghrelin and its receptor across the CNS and critically analyses the data available so far as regarding the effects of ghrelin on central neurotransmission

New pulsational properties of eight "anomalous" RR Lyrae variables

CCD photometry in the V band is presented for 7 field RR Lyrae stars selected from a sample of eight variables which, according to data collected in the literature, are expected to be {\it ab}-type pulsators, to have short periods and hence high metallicity, and to be located at high {\it z} from the galactic plane. New periods and epochs are derived for them. The new periods are only slightly shorter than the values published on the last edition of the General Catalog of Variable Stars (GCVS4). Instead, in six cases our amplitude of the light variation is significantly smaller than that published on the GCVS4, and in at least three cases the actual pulsation appears to be in the first harmonic rather than in the fundamental mode. All the suggested {\it c}-type pulsators show variations in the amplitude and/or quite scattered light curves. Possible explanations are given. From a spectro-photometric analysis of the sample, only DL Com is confirmed to pulsate in the fundamental mode, to have short period, and to be located at relatively high {\it z}. A single object cannot be taken as evidence for a significant metal rich population at large distance from the galactic plane.Comment: 28 pages including text and tables, plain tex. Figures available through anonymous ftp at ftp://astbo3.bo.astro.it/pub/bap/files/ (get bap95-12-fig1.ps and bap95-12-figures.ps

Anomalous RR Lyrae stars(?). III. CM Leonis

Time series of B,V,I CCD photometry and radial velocity measurements from high resolution spectroscopy (R=30,000) covering the full pulsation cycle are presented for the field RR Lyrae star CM Leonis. The photometric data span a 6 year interval from 1994 to 1999, and allow us to firmly establish the pulsation mode and periodicity of the variable. The derived period P=0.361699 days (+/- 0.000001) is very close to the value published in the Fourth Edition of the General Catalogue of Variable Stars (P=0.361732 days). However, contrary to what was previously found, the amplitude and shape of the light curve qualify CM Leo as a very regular first overtone pulsator with a prominent hump on the rising branch of its multicolour light curves. According to an abundace analysis performed on three spectra taken near minimum light (0.42 < phase < 0.61), CM Leo is a metal-poor star with metal abundance [Fe/H]=-1.93 +/- 0.20. The photometric and radial velocity curves of CM Leo have been compared with the predictions of suitable pulsational models to infer tight constraints on the stellar mass, effective temperature, and distance modulus of the star. We derive a true distance modulus of CM Leo of (m-M)0=13.11 +/- 0.02 mag and a corresponding absolute magnitude of Mv=0.47 +/- 0.04. This absolute magnitude, once corrected for evolutionary and metallicity effects, leads to a true distance modulus of the Large Magellanic Cloud of (m-M)0=18.43 +/- 0.06 mag, in better agreement with the long astronomical distance scale.Comment: 14 pages, 10 figures, accepted for publication in MNRA

Variable stars and stellar populations in Andromeda XXI: II. Another merged galaxy satellite of M31?

B and V time-series photometry of the M31 dwarf spheroidal satellite Andromeda XXI (And XXI) was obtained with the Large Binocular Cameras at the Large Binocular Telescope. We have identified 50 variables in And XXI, of which 41 are RR Lyrae stars (37 fundamental-mode RRab, and 4 first-overtone RRc, pulsators) and 9 are Anomalous Cepheids (ACs). The average period of the RRab stars ( = 0.64 days) and the period-amplitude diagram place And~XXI in the class of Oosterhoff II - Oosterhoff-Intermediate objects. From the average luminosity of the RR Lyrae stars we derived the galaxy distance modulus of (m-M)$_0$=$24.40\pm0.17$ mag, which is smaller than previous literature estimates, although still consistent with them within 1 $\sigma$. The galaxy color-magnitude diagram shows evidence for the presence of three different stellar generations in And~XXI: 1) an old ($\sim$ 12 Gyr) and metal poor ([Fe/H]=$-$1.7 dex) component traced by the RR Lyrae stars; 2) a slightly younger (10-6 Gyr) and more metal rich ([Fe/H]=$-$1.5 dex) component populating the red horizontal branch, and 3) a young age ($\sim$ 1 Gyr) component with same metallicity, that produced the ACs. Finally, we provide hints that And~XXI could be the result of a minor merging event between two dwarf galaxies.Comment: accepted for publications in Ap

A New Wood Surface Flame-Retardant Based on Poly-m-Aramid Electrospun Nanofibers

Poly(meta-phenylene isophtalamide) (PMIA) was processed via electrospinning to provide nanofibrous membranes with randomly and aligned fibers. Mechanical performance of such membranes was evaluated, applying a normalization procedure that takes into account the peculiar morphology of such complex substrate where voids can sum up to almost 80% of the sample volume. Random and aligned fibers membranes are applied onto wood panels to test their fire resistance in cone calorimetry when coated in polyaramidic thin nanofiber mats. Tests highlighted that random fibers provide a better fire protection, increasing Time to Ignition and decreasing the Fire Performance Index. Another important parameter affecting the performance is the adhesive system used to apply the nanofibers onto wood that is able to significantly modify the fire performance of the polyaramidic-coated wood panels. POLYM. ENG. SCI., 2019. (c) 2019 Society of Plastics Engineer