Neuronal oxidative injury in the development of the epileptic disease : a potential target for novel therapeutic approaches

Epileptic diseases affect about 50 million people in the world and approximately 30% of patients diagnosed with epilepsy are unresponsive to current medications. For these reasons, primary prevention of epilepsy represents one of the priorities in epilepsy research. Intracellular oxido-reductive (redox) state is well known to play a crucial role, contributing to the maintenance of the proper function of biomolecules. Therefore, oxidative stress results in functional cellular disruption and cellular damage and may cause subsequent cell death via oxidation of proteins, lipids, and nucleotides. Recently, the role of oxidative stress in the early stage and in the progression of epileptic disorders has begun to be recognized. The early molecular response to oxidative stress represents a short-term reversible phenomenon that precedes higher and irreversible forms of oxidation. This article reviews the current understanding of the epileptogenic phenomena related to seizure-induced oxidative injury as potential “critical period” therapeutic targets for the prevention of chronic epileptic disorder.peer-reviewe

Redox sensitivity of tyrosine hydroxylase activity and expression in dopaminergic dysfunction

Oxidant molecules generated during neuronal metabolism appear to play a significant role in the processes of aging and neurodegeneration. Increasing experimental evidence suggests the noteworthy relevance of the intracellular reduction-oxidation (redox) balance for the dopaminergic (DA-ergic) neurons of the substantia nigra pars compacta. These cells possess a distinct physiology intrinsically associated with elevated reactive oxygen species production, conferring on them a high vulnerability to free radical damage, one of the major causes of selective DA-ergic neuron dysfunction and degeneration related to neurological disorders such as Parkinson’s disease. Tyrosine hydroxylase (tyrosine 3-monooxygenase; E.C. 1.14.16.2; TH) activity represents the rate-limiting biochemical event in DA synthesis. TH activity, metabolism and expression are finely tuned by several regulatory systems in order to maintain a crucial physiological condition in which DA synthesis is closely coupled to its secretion. Alterations of these regulatory systems of TH functions have indeed been thought to be key events in the DA-ergic degeneration. TH has seven cysteine residues presenting thiols. Depending on the oxido-reductive (redox) status of the cellular environment, thiols exist either in the reduced form of free thiols or oxidized to disulfides. The formation of disulfides in proteins exerts critical regulatory functions both in physiological and in pathological conditions when oxidative stress is sustained. Several reports have recently shown that redox state changes of thiol residues, as consequence of an oxidative injury, can directly or indirectly affect the TH activity, metabolism and expression. The major focus of this review, therefore, is to report recent evidence on the redox modulation of TH activity and expression, and to provide an overview of a cellular phenomenon that might represent a target for new therapeutic strategies against the DA-ergic neurodegenerative disorders.peer-reviewe

5-HT2 receptors-mediated modulation of voltage-gated K+ channels and neurophysiopathological correlates

The activity of voltage-gated K(+) channels (Kv) can be dynamically modulated by several events, including neurotransmitter stimulated biochemical cascades mediated by G protein-coupled receptors such as 5-HT2 receptors (5-HT2Rs). Activation of 5-HT2A/CR inhibits the Shaker-like K(+) channels Kv1.1 and Kv1.2, and this modulation involves the dual coordination of both RPTPα and distinct tyrosine kinases coupled to this receptor; 5-HT2Rs-mediated modulation of Kv channels controls glutamate release onto prefrontal cortex neurons that might play critical roles in neurophysiological, neurological, and psychiatric conditions. Noticeably, hallucinogens modulate Kv channel activity, acting at 5-HT2R. Hence, comprehensive knowledge of 5-HT2R signaling through modulation of distinct K(+) channels is a pivotal step in the direction that will enable scientists to discover novel 5-HT functions and dysfunctions in the brain and to identify original therapeutic targets.peer-reviewe

Preferential modulation of the lateral habenula activity by serotonin-2A rather than -2C receptors: Electrophysiological and neuroanatomical evidence

Aims: Serotonergic (5-HT) modulation of the lateral habenula (LHb) activity is central in normal and pathologic conditions such as mood disorders. Among the multiple 5-HT receptors (5-HTRs) involved, the 5-HT2CR seems to play a pivotal role. Yet, the role of 5-HT2ARs in the control of the LHb neuronal activity is completely unknown. Methods: Single-cell extracellular recording of the LHb neurons was used in rats to study the effect of the general activation and blockade of the 5-HT2CR and 5-HT2AR with Ro 60-0175 and SB242084, TCB-2 and MDL11939, respectively. The expression of both receptors in the LHb was confirmed using immunohistochemistry. Results: Cumulative doses (5-640 \uce\ubcg/kg, iv) of Ro 60-0175 and TCB-2 affected the activity of 34% and 63% of the LHb recorded neurons, respectively. LHb neurons were either inhibited at low doses or excited at higher doses of the 5-HT2A/CR agonists. SB242084 or MDL11939 (both at 200 \uce\ubcg/kg, iv) did not modify neuronal firing when injected alone, but reverted the bidirectional effects of Ro 60-0175 or TCB-2, respectively. 5-HT2CRs and 5-HT2ARs are expressed in less than the 20% of the LHb neurons, and they neither colocalize nor make heterodimers. Strikingly, only 5-HT2ARs are expressed by the majority of LHb astrocyte cells. Conclusions: Peripheral administration of 5-HT2AR agonist promotes a heterogeneous pattern of neuronal responses in the LHb, and these effects are more prominent than those induced by the 5-HT2CR activation

Integrazione di tecniche di monitoraggio da terra e da satellite per lo studio di due frane a cinematica lenta

In questo lavoro è stata applicata una tecnica interferometrica sviluppata dal Departamento de Teoria del Senyal della UPC di Barcellona, basata sul principio dei Coherent Scatterers (Schneider et al., 2006), per la valutazione degli spostamenti superficiali nell’ambito del monitoraggio della frana di Costa della Gaveta (PZ). Tale algoritmo di tipo SBAS (Berardino et al., 2002, Lanari et al., 2004) denominato CPT (Coherent Pixels Technique – Mora et al., 2003) consente di calcolare le velocità medie di spostamento nell’intero periodo di osservazione. Il set di immagini utilizzato è quello relativo alla Track 086 Frame 798 in orbita ascending consistente in 24 immagini che coprono il periodo 2007- 2010. Tali risultati sono stati poi confrontati con le misure GPS effettuate in situ nello stesso periodo di monitoraggio

Statistical moments of power spectrum: a fast tool for the classification of seismic events recorded on volcanoes

Abstract. Spectral analysis has been applied to almost thousand seismic events recorded at Vesuvius volcano (Naples, southern Italy) in 2018 with the aim to test a new tool for a fast event classification. We computed two spectral parameters, central frequency and shape factor, from the spectral moments of order 0, 1, and 2, for each event at seven seismic stations taking the mean among the three components of ground motion. The analyzed events consist of volcano-tectonic earthquakes, low frequency events and unclassified events (landslides, rockfall, thunders, quarry blasts, etc.). Most of them are of low magnitude, and/or low maximum signal amplitude, therefore the signal to noise ratio is very different between the low noise summit stations and the higher noise stations installed at low elevation around the volcano. The results of our analysis show that volcano-tectonic earthquakes and low frequency events are easily distinguishable through the spectral moments values, particularly at seismic stations closer to the epicenter. On the contrary, unclassified events show the spectral parameters values distributed in a broad range which overlap both the volcano-tectonic earthquakes and the low frequency events. Since the computation of spectral parameters is extremely easy and fast for a detected event, it may become an effective tool for event classification in observatory practice

Riflessioni sulla cinematica di una grande colata attiva della valle del Basento

La nota riporta alcune considerazioni sul meccanismo di spostamento di una grande e lenta colata attiva della valle del fiume Basento, in Basilicata. Le principali caratteristiche cinematiche sono: uniformità di spostamento nelle sezioni trasversali del canale, velocità sensibilmente decrescente da monte verso valle, modeste variazioni stagionali di velocità. Tra le potenziali cause di spostamento, qui si esamina il possibile ruolo dell’erosione al piede esercitata dal corso d’acqua con l’ausilio di analisi numeriche 2D basate su metodi dell’equilibrio limite e agli elementi finiti

Improvement of Olive Oil Mechanical Extraction: New Technologies, Process Efficiency, and Extra Virgin Olive Oil Quality

Most of the recent technological innovations applied to the mechanical oil extraction process are aimed at improving virgin olive oil quality and yield. Extra virgin olive oil (EVOO) quality is mainly based on the qualitative/quantitative composition of monounsaturated fatty acids, volatile and phenolic compounds that are strictly related to the health and sensory properties of the product, with particular attention given to the fraction of secoiridoid derivatives and C5 and C6 volatile compounds. The different levels of concentration of these compounds are due to some important variables: agronomic and technological. The chapter explains the recent approaches and innovations introduced in the oil extraction process to improve the working efficiency of the production system and to obtain high‐quality extra virgin olive oils