Monitoraggio real-time della neurochimica corticale in topi liberi di muoversi durante il sonno, la privazione di sonno e la veglia medinte microdialisi in vivo e neurosensori amperometrici

Aim: for millennia, mankind has tried to understand the function and the importance of sleep and this is a mystery that biology has yet to solve. The purpose of this research was study neurochemistry during sleep, sleep deprivation and wakefulness by means of in-vivo microdialysis and amperometric neurosensors. Method: the neurochemistry of the brain was studied by the combination of electrochemical and microdialysis techniques, electroencephalographic (EEG) and electromyographic (EMG) recordings. The mice were implanted with three electrodes for electroencephalographic recordings and two microdialysis probes. During the experiment, samples were taken every 15 minutes and then analyzed by UHPLC/CD ORBITRAP that allows to analyze all the molecules present the sample. Moreover, the biochemical dynamics of Ascorbic Acid (AA) have been extensively studied both in vitro and in vivo by the development of a nanostructured amperometric microsensor decorated with multiwall carbonanotubes (MWCNTs). Results: through multiple experiments it was possible to study the variation in levels of cortical AA in freely moving mice during sleep and sleep deprivation, furthermore, the microdialysis technique, combined with EEG and EMG, allowed to monitor extracellular molecules (as neurotransmitters) that are involved in the neurochemistry of sleep, sleep deprivation and wakefulness. Conclusion: understand the biology that is the basis of sleep is the goal of many researchers. It seems to be involved in different processes such as learning and memory, also, his disorders are the basis of diseases (i.e. depression). This study allows, for the first time, to have an overview of the neurochemistry of sleep contribute, therefore, to better understanding of its mechanisms and functions and laying the groundwork for future studies

Editorial: Emerging heterocycles as bioactive compounds

Heterocycles represent a privileged scaffold due to their ability to interact with biological systems via heteroatoms. It is no coincidence that every year the Food and Drug Administration approves numerous new drugs that contain at least one heterocyclic system as active pharmacophoric part in their structure. Many heterocyclic compounds with therapeutic properties, including anticancer, antimicrobial, anti-inflammatory and so on, come from natural sources such as plants and animals, and medicinal chemists very often use them to study their chemical space and improve their biological activity. In fact, several efficient approaches for the formation of aromatic heterocyclic compounds and their derivatives have been described in the literature in the past, but the development of new green synthetic procedures and methodologies for their high-yield synthesis is increasingly in demand in drug discovery program. This Editorial collects recent research progress in the field of medicinal chemistry focused on the synthesis of new bioactive heterocycles of different types of activities, including anticancer, antibacterial and anti-inflammatory

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induces apoptosis in mouse nigrostriatal glia. Relevance to nigral neuronal death and striatal neurochemical changes.

Swiss mice were given 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 25 mg/kg/day, for 5 consecutive days and killed at different days after MPTP discontinuance. Decreases in striatal tyrosine hydroxylase activity and levels of dopamine and its metabolites were observed 1 day after MPTP discontinuance. Ascorbic acid and glutamate levels had increased, dehydroascorbic acid and GSH decreased, whereas catabolites of high-energy phosphates (inosine, hypoxanthine, xanthine, and uric acid) were unchanged. In addition, gliosis was observed in both striatum and substantia nigra compacta (SNc). Sections of SNc showed some terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL)-positive cells. Neurochemical parameters of dopaminergic activity showed a trend toward recovery 3 days after MPTP discontinuance. At this time point, TUNEL-positive cells were detected in SNc; some of them showed nuclei with neuronal morphology. A late (days 6-11) increase in striatal dopamine oxidative metabolism, ascorbic acid oxidative status, and catabolites of high-energy phosphates were observed concomitant with nigral neuron and nigrostriatal glial cell apoptotic death, as revealed by TUNEL, acridine orange, and Hoechst staining, and transmission electron microscopy. These data suggest that MPTP-induced activation/apoptotic death of glial cells plays a key role in the sequential linkage of neurochemical and cellular events leading to dopaminergic nigral neuron apoptotic death

Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep

By identifying endogenous molecules in brain extracellular fluid metabolomics can provide insight into the regulatory mechanisms and functions of sleep. Here we studied how the cortical metabolome changes during sleep, sleep deprivation and spontaneous wakefulness. Mice were implanted with electrodes for chronic sleep/wake recording and with microdialysis probes targeting prefrontal and primary motor cortex. Metabolites were measured using ultra performance liquid chromatography-high resolution mass spectrometry. Sleep/wake changes in metabolites were evaluated using partial least squares discriminant analysis, linear mixed effects model analysis of variance, and machine-learning algorithms. More than 30 known metabolites were reliably detected in most samples. When used by a logistic regression classifier, the profile of these metabolites across sleep, spontaneous wake, and enforced wake was sufficient to assign mice to their correct experimental group (pair-wise) in 80–100% of cases. Eleven of these metabolites showed significantly higher levels in awake than in sleeping mice. Some changes extend previous findings (glutamate, homovanillic acid, lactate, pyruvate, tryptophan, uridine), while others are novel (D-gluconate, N-acetyl-beta-alanine, N-acetylglutamine, orotate, succinate/methylmalonate). The upregulation of the de novo pyrimidine pathway, gluconate shunt and aerobic glycolysis may reflect a wake-dependent need to promote the synthesis of many essential components, from nucleic acids to synaptic membranes

Ultrastructural effects of sleep and wake on the parallel fiber synapses of the cerebellum

Multiple evidence in rodents shows that the strength of excitatory synapses in the cerebral cortex and hippocampus is greater after wake than after sleep. The widespread synaptic weakening afforded by sleep is believed to keep the cost of synaptic activity under control, promote memory consolidation, and prevent synaptic saturation, thus preserving the brain's ability to learn day after day. The cerebellum is highly plastic and the Purkinje cells, the sole output neurons of the cerebellar cortex, are endowed with a staggering number of excitatory parallel fiber synapses. However, whether these synapses are affected by sleep and wake is unknown. Here, we used serial block face scanning electron microscopy to obtain the full 3D reconstruction of more than 7000 spines and their parallel fiber synapses in the mouse posterior vermis. This analysis was done in mice whose cortical and hippocampal synapses were previously measured, revealing that average synaptic size was lower after sleep compared to wake with no major changes in synapse number. Here, instead, we find that while the average size of parallel fiber synapses does not change, the number of branched synapses is reduced in half after sleep compared to after wake, corresponding to similar to 16% of all spines after wake and similar to 8% after sleep. Branched synapses are harbored by two or more spines sharing the same neck and, as also shown here, are almost always contacted by different parallel fibers. These findings suggest that during wake, coincidences of firing over parallel fibers may translate into the formation of synapses converging on the same branched spine, which may be especially effective in driving Purkinje cells to fire. By contrast, sleep may promote the off-line pruning of branched synapses that were formed due to spurious coincidences

Chemico-biological characterization of Torpedino Di Fondi® tomato fruits. A comparison with San Marzano cultivar at two ripeness stages

Torpedino di Fondi (TF) is a hybrid tomato landrace developed in Sicily and recently introduced in the south Lazio area along with the classical San Marzano (SM) cultivar. The present study aimed at characterizing TF tomatoes at both pink and red ripening stages, and at comparing them with traditional SM tomatoes. A multidisciplinary approach consisting of morphological, chemical (FT‐ICR MS, NMR, HPLC, and spectrophotometric methods), and biological (antioxidant and antifungal in vitro activity) analyses was applied. Morphological analysis confirmed the mini‐ San Marzano nature and the peculiar crunchy and solid consistency of TF fruits. Pink TF tomatoes displayed the highest content of hydrophilic antioxidants, like total polyphenols (0.192 mg/g), tannins (0.013 mg/g), flavonoids (0.204 mg/g), and chlorophylls a (0.344 mg/g) and b (0.161 mg/g), whereas red TF fruits were characterized by the highest levels of fructose (3000 mg/100 g), glucose (2000 mg/100 g), tryptophan (2.7 mg/100 g), phenylalanine (13 mg/100 g), alanine (25 mg/100 g), and total tri‐unsaturated fatty acids (13% mol). Red SM fruits revealed the greatest content of lipophilic antioxidants, with 1234 mg/g of total carotenoids. In agreement with phenolics content, TF cultivar showed the greatest antioxidant activity. Lastly, red TF inhibited Candida species (albicans, glabrata and krusei) growth

Reconnaissance of 2016 Central Italy Earthquake Sequence

The Central Italy earthquake sequence nominally began on 24 August 2016 with a M6.1 event on a normal fault that produced devastating effects in the town of Amatrice and several nearby villages and hamlets. A major international response was undertaken to record the effects of this disaster, including surface faulting, ground motions, landslides, and damage patterns to structures. This work targeted the development of high-value case histories useful to future research. Subsequent events in October 2016 exacerbated the damage in previously affected areas and caused damage to new areas in the north, particularly the relatively large town of Norcia. Additional reconnaissance after a M6.5 event on 30 October 2016 documented and mapped several large landslide features and increased damage states for structures in villages and hamlets throughout the region. This paper provides an overview of the reconnaissance activities undertaken to document and map these and other effects, and highlights valuable lessons learned regarding faulting and ground motions, engineering effects, and emergency response to this disaster