Targeting neurosteroid synthesis as a therapy for schizophrenia-related alterations induced by early psychosocial stress

Background Cogent evidence has shown that schizophrenia vulnerability is enhanced by psychosocial stress in adolescence, yet the underpinnings of this phenomenon remain elusive. One of the animal models that best capture the relationship between juvenile stress and schizophrenia is isolation rearing (IR). This manipulation, which consists in subjecting rats to social isolation from weaning through adulthood, results in neurobehavioral alterations akin to those observed in schizophrenia patients. In particular, IR-subjected rats display a marked reduction of the prepulse inhibition (PPI) of the startle reflex, which are posited to reflect imbalances in dopamine neurotransmission in the nucleus accumbens (NAcc). We recently documented that the key neurosteroidogenic enzyme 5α-reductase (5αR) plays an important role in the dopaminergic regulation of PPI; given that IR leads to a marked down-regulation of this enzyme in the NAcc, the present study was designed to further elucidate the functional role of 5αR in the regulation of PPI of IR-subjected rats. Methods We studied the impact of the prototypical 5αR inhibitor finasteride (FIN) on the PPI deficits and NAcc steroid profile of IR-subjected male rats, in comparison with socially reared (SR) controls. Results FIN (25–100 mg/kg, i.p.) dose-dependently countered IR-induced PPI reduction, without affecting gating integrity in SR rats. The NAcc and striatum of IR-subjected rats displayed several changes in neuroactive steroid profile, including a reduction in pregnenolone in both SR and IR-subjected groups, as well as a decrease in allopregnanolone content in the latter group; both effects were significantly opposed by FIN. Conclusions These results show that 5αR inhibition counters the PPI deficits induced by IR, possibly through limbic changes in pregnenolone and/or allopregnanolone concentrations

Deep-MEG: spatiotemporal CNN features and multiband ensemble classification for predicting the early signs of Alzheimer's disease with magnetoencephalography

AbstractIn this paper, we present the novel Deep-MEG approach in which image-based representations of magnetoencephalography (MEG) data are combined with ensemble classifiers based on deep convolutional neural networks. For the scope of predicting the early signs of Alzheimer's disease (AD), functional connectivity (FC) measures between the brain bio-magnetic signals originated from spatially separated brain regions are used as MEG data representations for the analysis. After stacking the FC indicators relative to different frequency bands into multiple images, a deep transfer learning model is used to extract different sets of deep features and to derive improved classification ensembles. The proposed Deep-MEG architectures were tested on a set of resting-state MEG recordings and their corresponding magnetic resonance imaging scans, from a longitudinal study involving 87 subjects. Accuracy values of 89% and 87% were obtained, respectively, for the early prediction of AD conversion in a sample of 54 mild cognitive impairment subjects and in a sample of 87 subjects, including 33 healthy controls. These results indicate that the proposed Deep-MEG approach is a powerful tool for detecting early alterations in the spectral–temporal connectivity profiles and in their spatial relationships

Geomaterials and decay forms of the coastal towers of Piscinni and Foghe, Weastern Sardinia

[EN] The distribution of Coastal Towers in Sardinia testify that foreign invasions, which occurred several times over the centuries, were particularly frequent and dangerous. The beginning of the eighth century signed an increase of the attacks from the sea. The most of Coastal Towers were built in the period of Spanish rule, from 1583 to 1720. Despite numerous restorations over the years, many of these defensive structures are in critical conditions, some also affected by structural collapse. The building materials are closely related to local geological outcrops, and consist of sedimentary, magmatic and metamorphic rocks. Study of different lithotypes allowed assessing the vulnerability of different materials in different environmental conditions. Salts, transported by aerosols and deposited inside the porous structures, are the principal cause of decay of the building materials. Chemical-physical and mineralogical-petrographic analyses, performed on some Towers allowed making some general assessments on their conservation status and restoration projects.Carcangiu, G.; Meloni, P.; Palomba, M.; Cocco, O.; Sitzia, F.; Murru, A.; Carboni, M.... (2015). Geomaterials and decay forms of the coastal towers of Piscinni and Foghe, Weastern Sardinia. En Defensive architecture of the mediterranean: XV to XVIII centuries. Vol. I. Editorial Universitat Politècnica de València. 345-352. https://doi.org/10.4995/FORTMED2015.2015.1753OCS34535

Cardiovascular remodelling in female diabetic rats

Diabetic cardiomyopathy involves both cardiac and large vessels alterations in their biochemical and biomechanical properties. Part of these dysfunctions is due to ROS overproduction and advanced glycated end-products (AGEs) synthesis caused by high blood glucose concentrations (1). Epidemiological studies usually ignore sexgender outcomes of diabetes that has higher cardiovascular risk in women than in men (2). The aim of the present study was to assess the effects of diabetes on aorta, portal vein and myocardium morphology in females Wistar rats. Diabetes was induced by a single dose of streptozotocin 65 mg/kg, and, after 4 and half months, we evaluated the cardiovascular remodelling by light and transmission electron microscopy (TEM). Paraformaldehyde fixed samples of aorta and portal vein were stained with Masson Trichrome method (for collagen fibers), Weigert’s stain (for elastic fibers), Hematoxylin and Eosin (for nuclei), and underwent to morphometric analysis. TEM samples were prepared accordingly to common protocols. Morphometric analysis performed on diabetic aortas showed a reduction of tunica media thickness, but the internal diameter width or the lumen cross-area was unchanged compared to controls. The number of smooth muscle cells increased in tunica media of diabetic aortas. The main change observed in diabetic portal veins was a reduction of the area occupied by elastic fibers in tunica adventitia. TEM observations of papillary muscles did not reveal any changes in the sarcomere lengths across the two experimental groups. These results display slight differences on what was reported in male rats (3) and account for a different development of diabetes in female subjects

Durability of repair mortars used in restoration of a Sardinian coastal tower: assessment after ten years

[EN] This study reports the results of investigations on conservation conditions of an ancient tower, called Torre del Pozzo, located in the S-W coast of Sardinia, restored about ten years ago. The tower suffers from serious problems related to vulnerability of building materials, particularly limestone and sandstones and aerial lime mortar with poor physical-mechanical properties. Over the centuries the materials were subjected to aggressive actions (wind corrasion and salt crystallization) causing an intense erosion of the walls with consequent partial collapse of the structure. About ten years ago a restoration involved the mortars and only the replacement and integration of ashlars deteriorated. After about 10 years from this intervention, some inspections have been carried out in order to assess the effectiveness of the intervention and the state of preservation of the tower. This paper focuses on analyses and tests carried out to assess condition and durability of the repair mortars.Meloni, P.; Carcangiu, G.; Palomba, M.; Enzo, S.; Carboni, M.; Cocco, O.; Casti, M.... (2015). Durability of repair mortars used in restoration of a Sardinian coastal tower: assessment after ten years. En Defensive architecture of the mediterranean: XV to XVIII centuries. Vol. II. Editorial Universitat Politècnica de València. 397-44. https://doi.org/10.4995/FORTMED2015.2015.1761OCS3974

The aggression and behavioral abnormalities associated with monoamine oxidase A deficiency are rescued by acute inhibition of serotonin reuptake

The termination of serotonin (5-hydroxytryptamine, 5-HT) neurotransmission is regulated by its uptake by the 5-HT transporter (5-HTT), as well as its degradation by monoamine oxidase (MAO)-A. MAO-A deficiency results in a wide set of behavioral alterations, including perseverative behaviors and social deficits. These anomalies are likely related to 5-HTergic homeostatic imbalances; however, the role of 5-HTT in these abnormalities remains unclear. To ascertain the role of 5-HTT in the behavioral anomalies associated to MAO-A deficiency, we tested the behavioral effects of its blocker fluoxetine on perseverative, social and aggressive behaviors in transgenic animals with hypomorphic or null-allele MAO-A mutations. Acute treatment with 5-HTT blocker fluoxetine (10 mg/kg, i.p.) reduced aggressive behavior in MAO-A knockout (KO) mice and social deficits in hypomorphic MAO-ANeo mice. Furthermore, this treatment also reduced perseverative responses (including marble burying and water mist-induced grooming) in both MAO-A mutant genotypes. Both MAO-A mutant lines displayed significant reductions in 5-HTT expression across the prefrontal cortex, amygdala and striatum, as quantified by immunohistochemical detection; however, the down-regulation of 5-HTT in MAO-ANeo mice was more pervasive and widespread than in their KO counterparts, possibly indicating a greater ability of the hypomorphic line to enact compensatory mechanisms with respect to 5-HT homeostasis. Collectively, these findings suggest that the behavioral deficits associated with low MAO-A activity may reflect developmental alterations of 5-HTT within 5-HTergic neurons. Furthermore, the translational implications of our results highlight 5-HT reuptake inhibition as an interesting approach for the control of aggressive outbursts in MAO-A deficient individuals

Enhanced endocannabinoid-mediated modulation of rostromedial tegmental nucleus drive onto dopamine neurons in sardinian alcohol-preferring rats

The progressive predominance of rewarding effects of addictive drugs over their aversive properties likely contributes to the transition from drug use to drug dependence. By inhibiting the activity of DA neurons in the VTA, GABA projections from the rostromedial tegmental nucleus (RMTg) are well suited to shift the balance between drug-induced reward and aversion. Since cannabinoids suppress RMTg inputs to DA cells and CB1 receptors affect alcohol intake in rodents, we hypothesized that the endocannabinoid system, by modulating this pathway, might contribute to alcohol preference. Here we found that RMTg afferents onto VTA DA neurons express CB1 receptors and display a 2-arachidonoylglycerol (2-AG)-dependent form of short-term plasticity, that is, depolarization-induced suppression of inhibition (DSI). Next, we compared rodents with innate opposite alcohol preference, the Sardinian alcohol-preferring (sP) and alcohol-nonpreferring (sNP) rats. We found that DA cells from alcohol-naive sP rats displayed a decreased probability of GABA release and a larger DSI. This difference was due to the rate of 2-AG degradation. In vivo, we found a reduced RMTg-induced inhibition of putative DA neurons in sP rats that negatively correlated with an increased firing. Finally, alcohol failed to enhance RMTg spontaneous activity and to prolong RMTg-induced silencing of putative DA neurons in sP rats. Our results indicate functional modifications of RMTg projections to DA neurons that might impact the reward/aversion balance of alcohol attributes, which may contribute to the innate preference observed in sP rats and to their elevated alcohol intak

Methodological approach in the conservation of coastal fortifications

[EN] The historical and artistic value of Coastal Towers justifies the recovery of these emblematic artifacts. For the achievement of this objective we propose a methodological approach including: i) architectural relief also by 3D laser scanner and collection of historical data; ii) macroscopic semi-quantitative evaluation of the decay, iii) application of diagnostic quantitative chemical-physical-mechanical methodologies, to assess the decay intensity, and define the criticalities for planning the restoration. The i step allows the graphic rendering of the building showing the geometry and the relationships between the parties. The ii step allows a preliminary understanding of the building materials, macroscopic alteration forms, monument features, acquisition of information about potential causes and decay mechanisms. During the iii step, sampling of building materials is planned. Laboratory analyses, to determine the soluble salts, crystalline phases, porosity as well as micro-textural features of the materials, are carried out by the application of suitable techniques.Carcangiu, G.; Columbu, S.; Meloni, P.; Carboni, M.; Casti, M.; Cocco, O.; Murru, A.... (2015). Methodological approach in the conservation of coastal fortifications. En Defensive architecture of the mediterranean: XV to XVIII centuries. Vol. I. Editorial Universitat Politècnica de València. 341-344. https://doi.org/10.4995/FORTMED2015.2015.1752OCS34134

Lista bibliografica

Questa lista bibliografica contiene il secondo aggiornamento della bibliografia della Lisy e deriva dall’assemblaggio da parte della redazione (M. Serdoz ed E. Panfili) dei contributi parziali stilati dai gruppi regionali