Publications by authors named "Vincenza D'angelo"

Background: The accumulation of α-synuclein (α-syn) fibrils in intraneuronal inclusions called Lewy bodies and Lewy neurites is a pathological signature of Parkinson's disease (PD). Although several aspects linked to α-syn-dependent pathology (concerning its spreading, aggregation, and activation of inflammatory and neurodegenerative processes) have been under intense investigation, less attention has been devoted to the real impact of α-syn overexpression on structural and functional properties of substantia nigra pars compacta (SNpc) dopamine (DA) neurons, particularly at tardive stages of α-syn buildup, despite this has obvious relevance to comprehending mechanisms beyond PD progression.

Objectives: We aimed to determine the consequences of a prolonged α-syn overexpression on somatodendritic morphology and functions of SNpc DA neurons.

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Parkinson's disease (PD) is a neurodegenerative disease characterized by the accumulation of alpha-synuclein, encoded by the gene. The main neuropathological hallmark of PD is the degeneration of dopaminergic neurons leading to striatal dopamine depletion. Trophic support by a neurotrophin called glial-derived neurotrophic factor (GDNF) is also lacking in PD.

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We aimed to investigate A2A receptors in the basal ganglia of a DYT1 mouse model of dystonia. A2A was studied in control Tor1a+/+ and Tor1a+/- knock-out mice. A2A expression was assessed by anti-A2A antibody immunofluorescence and Western blotting.

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Pyroptosis is a type of cell death that is caspase-1 (Casp-1) dependent, which leads to a rapid cell lysis, and it is linked to the inflammasome. We recently showed that pyroptotic cell death occurs in Huntington's disease (HD). Moreover, we previously described the beneficial effects of a PARP-1 inhibitor in HD.

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The history of deep brain stimulation for Parkinson's disease (PD) represented a paradigmatic cross-talk between mammalian disease models and clinical evidence in humans. Fascinating were the results achieved by high frequency stimulation (HFS) into the subthalamic nucleus (STN) of MPTP-treated primates. An analogous strategy relieved tremor and hypokinetic parameters in PD patients.

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Mechanisms of tissue damage in Huntington's disease involve excitotoxicity, mitochondrial damage, and neuroinflammation, including microglia activation. In the present study, we investigate the role of pyroptosis process in the striatal neurons of the R6/2 mouse model of Huntington's disease. Transgenic mice were sacrificed at 4 and 13 weeks of age.

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Introduction: Increasing evidence demonstrates the relevant association between Parkinson's disease (PD) and vascular diseases/risk factors, as well as a worse clinico-pathological progression in those patients with vascular comorbidity. The mechanisms underlying this relationship have not been clarified yet, although their comprehension is critical in a perspective of disease-modifying treatments development or prevention.

Methods: We performed an experimental protocol of ischemic injury (glucose-oxygen deprivation, OGD) on PTEN-induced kinase 1 knockout (PINK1) mice, a well-established PD model, looking at both electrophysiological and morphological changes in basal ganglia.

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Dystonia pathophysiology has been partly linked to downregulation and dysfunction ofdopamine D2 receptors in striatum. We aimed to investigate the possible morpho-structuralcorrelates of D2 receptor downregulation in the striatum of a DYT1 Tor1a mouse model. Adultcontrol Tor1a+/+ and mutant Tor1a+/- mice were used.

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Mechanisms of tissue damage in Huntington's disease involve excitotoxicity, mitochondrial damage, and inflammation, including microglia activation. Immunomodulatory and anti-protein aggregation properties of tetracyclines were demonstrated in several disease models. In the present study, the neuroprotective and anti-inflammatory effects of the tetracycline doxycycline were investigated in the mouse model of HD disease R6/2.

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Poly (ADP-ribose) polymerases (PARPs) are enzymes that catalyze ADP-ribose units transfer from NAD to their substrate proteins. It has been observed that PARP-1 is able to increase both post-ischemic and excitotoxic neuronal death. In fact, we have previously shown that, INO-1001, a PARP-1 inhibitor, displays a neuroprotective effect in the R6/2 model of Huntington's disease (HD).

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We report that changes of phosphodiesterase-10A (PDE10A) can map widespread functional imbalance of basal ganglia circuits in a mouse model of DYT1 dystonia overexpressing mutant torsinA. PDE10A is a key enzyme in the catabolism of second messenger cAMP and cGMP, whose synthesis is stimulated by D1 receptors and inhibited by D2 receptors preferentially expressed in striatoentopeducuncular/substantia nigra or striatopallidal pathways, respectively. PDE10A was studied in control mice (NT) and in mice carrying human wild-type torsinA (hWT) or mutant torsinA (hMT).

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In Parkinson's disease (PD), several efforts have been spent in order to find biochemical parameters able to identify the progression of the pathological processes at the basis of the disease. It is already known that advanced PD patients manifesting dyskinesia are featured by the high homovanillic acid (HVA)/dopamine (DA) ratio, suggesting the increased turnover of DA in these patients. Less clear is whether similar changes affect mild and moderate stages of the disease (between 1 and 2.

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Enhanced β band (βB) activity, which is suppressed by levodopa (LD) treatment, has been demonstrated within the basal ganglia (BG) of Parkinson's disease (PD) patients. However, some data suggest that Parkinsonian symptoms are not directly related to this brain frequency and therefore, its causative role remains questionable. A less explored phenomenon is the link between the γ band (γB) and PD phenomenology.

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In Alzheimer disease, the gap between excellence of diagnostics and efficacy of therapy is wide. Despite sophisticated imaging and biochemical markers, the efficacy of available therapeutic options is limited. Here we examine the possibility that assessment of endogenous catecholamine levels in cerebrospinal fluid (CSF) may fuel new therapeutic strategies.

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Second messenger cAMP and cGMP represent a key step in the action of dopamine that modulates directly or indirectly their synthesis. We aimed to verify whether levodopa-induced dyskinesias are associated with changes of the time course of levodopa/dopamine stimulated cAMP and cGMP levels, and/or with changes of their catabolism by phosphodiesterase activity in rats with experimental hemiparkinsonism. Microdialysis and tissue homogenates of the striatal tissues demonstrated that extracellular and intracellular cAMP/cGMP levels were lower in dyskinetic animals during the increasing phase of dyskinesias compared to eukinetic animals, but cAMP/cGMP levels increased in dyskinetic animals during the phase of decreasing and extinction of dyskinesias.

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In Parkinson's disease (PD), several studies have detected an impaired serotonin (5-HT) pathway, likely affecting both motor and non-motor domains. However, the precise impact of 5-HT impairment is far from established. Here, we have used a HPLC chromatographic method, in a homogenous cohort (n = 35) of non fluctuating, non dyskinetic PD patients, to assess the concentration of 5-HT and its metabolite 5-HIAA in peripheral cerebrospinal fluid (CSF) obtained from lumbar puncture (LP).

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Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an efficacious therapy for Parkinson's disease (PD) but its effects on non-motor facets may be detrimental. The low-frequency stimulation (LFS) of the pedunculopontine nucleus (PPN or the nucleus tegmenti pedunculopontini - PPTg-) opened new perspectives. In our hands, PPTg-LFS revealed a modest influence on gait but increased sleep quality and degree of attentiveness.

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It has been recently shown that the substantia nigra pars reticulata (SNr) of 6-hydroxydopamine (6-OHDA)-lesioned rats, under urethane anaesthesia, manifests a prominent low frequency oscillation (LFO) of around 1Hz, synchronized with cortical slow wave activity (SWA). Nevertheless, it is poorly understood whether these electrophysiological alterations are correlated only with severe dopamine depletion or may also play a relevant pathogenetic role in the early stages of the dopamine denervation. Hence, here we recorded SNr single units and electrocorticogram (ECoG) in two models of dopamine denervation: (i) acute dopamine denervated rats, obtained by injection of tetrodotoxin (TTX), (ii) chronic dopamine depleted rats, 2 weeks after 6-OHDA lesioning.

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Pathological oscillations characterize the firing discharge of different basal ganglia (BG) stations in rat models of Parkinson's disease. Most recent literature focused on the prominence of the beta frequency band in awake rats. Yet, in 6-hydroxydopamine-lesioned animals, the firing discharge of the globus pallidus (GP) and the substantia nigra reticulata are in phase with urethane-induced slow wave cortical activity.

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Within the striatum, the gaseous neurotransmitter nitric oxide (NO) is produced by a subclass of interneurons containing the neuronal NO synthase (nNOS). NO promotes the second messenger cGMP through the activation of the soluble guanyl cyclase (sGC) and plays a crucial role in the integration of glutamate (GLU) and DA transmission. The aim of this study was to characterize the impact of 6-hydroxyDA (6-OHDA) lesion of the rat nigrostriatal pathway on NO/cGMP system.

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The tridecapeptide neurotensin (NT) is involved in the modulation of dopamine (DA)-mediated functions in the nigrostriatal and mesocorticolimbic pathways. Its relevance in mammalian globus pallidus (GP) is questioned. A recent electrophysiological study on GP slices described NT-mediated robust membrane depolarization, depending upon the suppression of potassium conductance and/or the activation of cation current.

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Recent evidence has shown that the activity of cAMP responsive element-binding protein (CREB) and of CREB-binding protein (CBP) is decreased in Huntington's disease (HD) [Steffan et al. (2000)Proc. Natl Acad.

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Dopamine and NO are physiological stimulators of synthesis of cAMP and cGMP, respectively, and NO synthase-containing interneurons in the striatum are physiologically activated by dopamine-containing neurons in the substantia nigra. This study investigated whether lesioning dopamine neurons has multiple consequences in the striatum consistent with the reported sensitization of cAMP synthesis, including alteration of the NO-cGMP pathway and phosphodiesterase-dependent metabolism of cyclic nucleotides. The substantia nigra of adult Sprague-Dawley rats was unilaterally lesioned with 6-hydroxydopamine.

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Previous work has shown that enkephalins target N-type calcium (Ca2+) channels in striatal and globus pallidus (GP) neurons, principally through activation of mu-like receptors. Here, we examined the effects of selective mu, delta, and kappa agonists on Ca2+ currents in striatal and GP neurons isolated from either control or reserpine-treated rats. In cells from control rats DAMGO and dynorphin (DYN) inhibited high-voltage-activated (HVA) Ca2+ currents preferentially in "medium-to-small" GP cells (likely to correspond to parvalbumin-negative cells).

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