Mantle upwelling beneath the Apennines identified by receiver function imaging.

Magmatism, uplift and extension diffusely take place along collisional belts. Even though links between mantle dynamics and shallow deformation are becoming more evident, there is still poor understanding of how deep and surface processes are connected. In this work, we present new observations on the structure of the uppermost mantle beneath the Apennines belt. Receiver functions and seismic tomography consistently define a broad zone in the shallow mantle beneath the mountain belt where the shear wave velocities are lower than about 5% and the Vp/Vs ratio is higher than 3% than the reference values for these depths. We interpret these anomalies as a pronounced mantle upwelling with accumulation of melts at the crust-mantle interface, on top of which extensional seismicity responds to the crustal bending. The melted region extends from the Tyrrhenian side to the central part of the belt, with upraise of fluids within the crust favored by the current extension concentrated in the Apennines mountain range. More in general, mantle upwelling, following detachment of continental lithosphere, is a likely cause for elevated topography, magmatism and extension in post-collisional belts.

Probing crustal anisotropy by receiver functions at the deep continental drilling site KTB in Southern Germany.

Seismic anisotropy is a unique observational tool for remotely studying deformation and stress within the Earth. Effects of anisotropy can be seen in seismic data; they are due to mineral alignment, fractures or layering. Seismic anisotropy is linked to local stress and strain, allowing modern geophysics to derive geomechanical properties from seismic data for supporting well planning and fracking. For unravelling anisotropic properties of the crust, the teleseismic receiver functions methodology has started to be widely applied recently due to its ability in retrieving the three-dimensional characteristics of the media sampled by the waves. The applicability of this technique is tested here by a field test carried out around the Kontinental Tiefbohrung site in southeastern Germany. We compare our results to previous investigations of the metamorphic rock pile of the Zone Erbendorf-Vohenstrauss, drilled down to 9 km depth, which sampled an alternating sequence of paragneiss and amphibolite, in which a strong foliation has been produced by ductile deformation. The application of the receiver functions reveals the presence of two distinct anisotropic layers within the metamorphic rock pile at 0-4 km and below 6 km depth, with up to 8% anisotropy; the depth of these two layers corresponds to the location of mica-rich paragneiss which show intense foliation, and finally proves the relation between the signal in the receiver functions, rock texture and presence of cracks. We have now the capability of providing insights from passive seismic data on geomechanical properties of the rocks, useful for geological exploration and engineering purposes, which will help influencing expensive drilling decisions thanks to future application of this seismic technique.

Slab detachment under the Eastern Alps seen by seismic anisotropy.

We analyze seismic anisotropy for the Eastern Alpine region by inspecting shear-wave splitting from SKS and SKKS phases. The Eastern Alpine region is characterized by a breakdown of the clear mountain-chain-parallel fast orientation pattern that has been previously documented for the Western Alps and for the western part of the Eastern Alps. The main interest of this paper is a more detailed analysis of the anisotropic character of the Eastern Alps, and the transition to the Carpathian-Pannonian region. SK(K)S splitting measurements reveal a rather remarkable lateral change in the anisotropy pattern from the west to the east of the Eastern Alps with a transition area at about 12°E. We also model the backazimuthal variation of the measurements by a vertical change of anisotropy. We find that the eastern part of the study area is characterized by the presence of two layers of anisotropy, where the deeper layer has characteristics similar to those of the Central Alps, in particular SW-NE fast orientations of anisotropic axes. We attribute the deeper layer to a detached slab from the European plate. Comparison with tomographic studies of the area indicates that the detached slab might possibly connect with the lithosphere that is still in place to the west of our study area, and may also connect with the slab graveyard to the East, at the depth of the upper mantle transition zone. On the other hand, the upper layer has NW-SE fast orientations coinciding with a low-velocity layer which is found above a more-or-less eastward dipping high-velocity body. The anisotropy of the upper layer shows large-scale NW-SE fast orientation, which is consistent with the presence of asthenospheric flow above the detached slab foundering into the deeper mantle.

Insights on the upper mantle beneath the Eastern Alps.

Analyses of Ps and Sp receiver functions from datasets collected by permanent and temporary seismic stations, image a seismic discontinuity, due to a negative velocity contrast across the entire Eastern Alps. The receiver functions show the presence of the discontinuity within the upper mantle with a resolution of tens of kilometers laterally. It is deeper (100-130 km) below the central portion of the Eastern Alps, and shallower (70-80 km) towards the Pannonian Basin and in the Central Alps. Comparison with previous studies renders it likely that the observed discontinuity coincides with the lithosphere-asthenosphere boundary (LAB) east of 15°E longitude, while it could be associated with a low velocity zone west of 15°E.

Pramipexole prevents neurotoxicity induced by oligomers of beta-amyloid.

Here we demonstrate that pramipexole, an antiparkinsonian dopamine receptor agonist drug, exerts neuroprotective effects against beta-amyloid neurotoxicity. Using a specific protocol to test individually oligomers, fibrils, or unaggregated amyloid beta-peptide, we found pramipexole able to protect cells against oligomers and fibrils. Unaggregated amyloid beta-peptide was found unable to cause cell death. Fibrils and oligomers were also found to produce elevated amount of free radicals, and this effect was prevented by pramipexole. We propose pramipexole may become in the future a coadjuvant in the treatment of neuropathologies, besides Parkinson's disease, where amyloid beta-peptide-mediated oxidative injury exerts a relevant role.

Glucocorticoid inhibition of growth in rats: partial reversal with the full-length ghrelin analog BIM-28125.

Glucocorticoids are important immunosuppressive hormones; these steroids also inhibit somatic growth by decreased growth hormone (GH) secretion and induced protein catabolism. The ability of ghrelin, the endogenous ligand for the GHS-1a receptor, to increase body weight is attributed to a combination of enhanced food intake, increased gastric emptying and increased food assimilation, coupled with potent GH releasing activity. The aim of the present study was to evaluate the ability of a full-length, metabolically stabilized ghrelin agonist, BIM-28125, to reverse the dexamethasone-induced decrease of growth rate of prepubertal Sprague-Dawley male rats. Twenty-one days old rats were randomly assigned to two treatment groups. Beginning on day 23 of age, 16 animals were treated ip either with saline or DEX (40 microg/kg/day). On day 33 after birth, these two groups were further subdivided and treated sc with either vehicle or BIM-28125 (80 nmol/kg, t.i.d.). On day 47 after birth, rats were killed and trunk blood was collected for hormone determinations. DEX significantly reduced final body weight and nose-anal length; BIM-28125 increased linear growth in saline-treated rats and reversed growth inhibition in DEX-treated rats. The inhibitory effects of DEX on somatic growth was paralleled by decreased 24 h food intake (FI), decreased food efficiency (FE) and lower plasma IGF-1 levels versus vehicle-treated rats. BIM-28125 induced an increase of FI, FE and plasma IGF-1 in saline-treated rats, and reversed the inhibitory effects of DEX. These preclinical results leads to the conclusion that BIM-28125 may represent a good tool to reverse the catabolic effects induced by glucocorticoids.

Dopaminergic agonists: possible neurorescue drugs endowed with independent and synergistic multisites of action.

Dopaminergic agonists have been usually used as adjunctive therapy for the cure of Parkinson's disease (PD). It is generally believed that treatment with these drugs is symptomatic rather then curative and does not stop or delay the progression of neuronal degeneration. However, several DA agonists of the DA D2-receptor family (including D2, D3 and D4-subtypes) have recently been shown to possess neuroprotective properties in different in vitro and in vivo experimental PD models. Here we summarize some recent data from our and other groups underlining the wide pharmacological spectrum of DA agonists currently used for treating PD patients. In particular, the mechanism of action of different DA agonists does not appear to be restricted to the stimulation of selective DA receptor subtypes being these drugs endowed with intrinsic, independent, and peculiar antioxidant effects. This activity may represent an additional pharmacological property contributing to their clinical efficacy in PD.

Clozapine-induced alteration of glucose homeostasis in the rat: the contribution of hypothalamic-pituitary-adrenal axis activation.

BACKGROUND/AIMS: To our knowledge, a suitable animal model to investigate how atypical antipsychotics may induce diabetes in patients has not received much attention. METHODS: We investigated the effects of acute as well as subchronic administration of clozapine on food intake, body weight gain, glucose tolerance and insulin secretion in response to glucose in Sprague-Dawley rats. We then evaluated the effects of clozapine on corticosterone secretion and 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) and phosphoenolpyruvate carboxykinase (PEPCK) expression in the liver. We investigated the in vitro effects of clozapine on glucose uptake and development of differentiated myotubes in skeletal muscle cell (C2C12) cultures. RESULTS: Clozapine administration caused hyperglycemia (p < 0.05) in female rats. In male rats, the increase of plasma glucose levels after clozapine injection was not statistically significant. The increase of plasma insulin concentrations and the intraperitoneal glucose tolerance test results proved that clozapine reduced insulin sensitivity in female rats. These endocrine and metabolic effects of clozapine were not related to changes in feeding behavior of fat accumulation. We observed a stimulatory effect of clozapine on corticosterone (p < 0.01) secretion in both female and male rats. Chronic clozapine administration upregulated PEPCK and 11beta-HSD-1 expression in rat liver. Clozapine did not inhibit basal and insulin-induced glucose transport in murine myotubes but it was able to antagonize the stimulatory effect of alpha-methyl-5-hydroxytryptamine on glucose uptake. CONCLUSION: Clozapine induces sex-related alterations of glucose homeostasis and insulin sensitivity in rodents. We discussed the possible contribution of clozapine-induced activation of HPA and clozapine antagonistic activity at peripheral 5-HT(2A) receptors to the observed metabolic alterations.