A5017071544- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Nicotinic Acetylcholine Receptors Study
- Nuclear Receptors and Signaling
- Genetics and Neurodevelopmental Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Autism Spectrum Disorder Research
- Neural dynamics and brain function
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Memory and Neural Mechanisms
- Adenosine and Purinergic Signaling
- Cholinesterase and Neurodegenerative Diseases
- Neurogenesis and neuroplasticity mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Tryptophan and brain disorders
- Neuroscience and Neural Engineering
- Autoimmune Neurological Disorders and Treatments
- Cytokine Signaling Pathways and Interactions
- Inflammasome and immune disorders
- Histone Deacetylase Inhibitors Research
- Amino Acid Enzymes and Metabolism
- Dementia and Cognitive Impairment Research
- Epigenetics and DNA Methylation
- Functional Brain Connectivity Studies
Fondazione Santa Lucia
2016-2025
Università Campus Bio-Medico
2019-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2015-2024
University of Rome Tor Vergata
2014-2018
University College London
2009-2011
Alterations of the dopaminergic (DAergic) system are frequently reported in Alzheimer's disease (AD) patients and commonly linked to cognitive non-cognitive symptoms. However, cause DAergic dysfunction AD remains be elucidated. We investigated alterations midbrain Tg2576 mouse model AD, overexpressing a mutated human amyloid precursor protein (APPswe). Here, we found an age-dependent neuron loss ventral tegmental area (VTA) at pre-plaque stages, although substantia nigra pars compacta (SNpc)...
Neuroinflammation is one of the hallmarks Parkinson's disease (PD) and may contribute to midbrain dopamine (DA) neuron degeneration. Recent studies link chronic inflammation with failure resolve early inflammation, a process operated by specialized pro-resolving mediators, including resolvins. However, effects stimulating resolution in PD - modulate progression still remain unexplored. Here we show that rats overexpressing human α-synuclein (Syn) display altered DA properties, reduced...
Abstract Early and progressive dysfunctions of the dopaminergic system from Ventral Tegmental Area (VTA) have been described in Alzheimer’s Disease (AD). During long pre-symptomatic phase, alterations function Parvalbumin interneurons (PV-INs) are also observed, resulting cortical hyperexcitability represented by subclinical epilepsy aberrant gamma-oscillations. However, it is unknown whether deficits contribute to brain AD. Here, using Tg2576 mouse model AD, we prove that reduced...
What happens precociously to the brain destined develop Alzheimer's Disease (AD) still remains be elucidated and this is one reason why effective AD treatments are missing. Recent experimental clinical studies indicate that degeneration of dopaminergic (DA) neurons in Ventral Tegmental Area (VTA) could first events occurring AD. However, causes increased vulnerability DA Here, we deeply investigate physiology VTA before, at onset, after onset neurodegeneration. We use Tg2576 mouse model AD,...
Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by pronounced social and communication deficits stereotyped behaviours. Recent psychosocial neuroimaging studies have highlighted reward-processing reduced dopamine (DA) mesolimbic circuit reactivity in ASD patients. However, the neurobiological molecular determinants of these remain undetermined. Mouse models recapitulating ASD-like phenotypes could help generate hypotheses about origin neurophysiological...
OPINION article Front. Mol. Neurosci., 17 May 2019Sec. Brain Disease Mechanisms Volume 12 - 2019 | https://doi.org/10.3389/fnmol.2019.00123
Abstract We studied the properties of dopaminergic neurons in substantia nigra pars compacta ( SN pc) and ventral tegmental area VTA ) mice expressing enhanced green fluorescent protein eGFP under control tyrosine hydroxylase promoter TH ‐ GFP ). By using a practical map cell positioning distinct pc subregions horizontal midbrain slices we saw that spontaneous firing, membrane properties, body size magnitude hyperpolarization‐activated current I h ‐positive + vary significantly among...
Recent clinical and experimental studies have highlighted the involvement of Ventral Tegmental Area (VTA) dopamine (DA) neurons for early pathogenesis Alzheimer's Disease (AD). We previously described a progressive selective degeneration these in Tg2576 mouse model AD, long before amyloid-beta plaque formation. The degenerative process DA is associated with an autophagy flux impairment, whose rescue can prevent neuronal loss. Impairments be basis accumulation damaged mitochondria, leading to...
Neuropsychiatric symptoms (NPS) occur in nearly all patients with Alzheimer's Disease (AD). Most frequently they appear since the mild cognitive impairment (MCI) stage preceding clinical AD, and have a prognostic importance. Unfortunately, these also worsen daily functioning of patients, increase caregiver stress accelerate disease progression from MCI to AD. Apathy depression are most common NPS, much attention has been given recent years understand biological mechanisms related their...
Among the genomic alterations identified as risk factors in mice models of autism spectrum disorders (ASD), heterozygous deletion Ambra1 (Activating Molecule Beclin1-Regulated Autophagy) triggers an ASD phenotype associated with hippocampal hyperexcitability exclusively female sex although protein is comparably expressed hippocampus symptomatic females and asymptomatic males. Given intricate relationship between deficiency etiology ASD, we took advantage including Ambra1+/− males wild-type...
Background The neuronal nicotinic receptors that mediate excitatory transmission in autonomic ganglia are thought to be formed mainly by the α3 and β4 subunits. Expressing this composition oocytes fails reproduce properties of ganglionic receptors, which may also incorporate α5 and/or β2 We compared human α3β4 expressed Human embryonic kidney cells (HEK293) Xenopus oocytes, examine effect expression system α∶β subunit ratio. Methodology/Principal Findings Two distinct channel forms were...
Clinical and neuropathological studies have shown that tau pathology better correlates with the severity of dementia than amyloid plaque burden, making an attractive target for cure Alzheimer's disease. We explored whether passive immunization 12A12 monoclonal antibody (26-36aa protein) could improve disease phenotype two well-established mouse models, Tg2576 3xTg mice. is a cleavage-specific which selectively binds pathologically relevant neurotoxic NH226-230 fragment (i.e. NH2htau) protein...
Abstract The last decades have witnessed huge efforts devoted to deciphering the pathological mechanisms underlying Alzheimer’s Disease (AD) and testing new drugs, with recent FDA approval of two anti-amyloid monoclonal antibodies for AD treatment. Beyond these drug-based experimentations, a number pre-clinical clinical trials are exploring benefits alternative treatments, such as non-invasive stimulation techniques on neuropathology symptoms. Among different brain approaches, transcranial...
The β3 neuronal nicotinic subunit is localized in dopaminergic areas of the central nervous system, which many other subunits are expressed. So far, has only been shown to form functional receptors when expressed together with α3 and β4 subunits. We have systematically tested <i>Xenopus laevis</i> oocytes effects coexpressing human every pairwise combination likely be relevant system. Expression α7 homomers or α/β pairs (α2, α3, α4, α6 β2 β4) produced robust currents for all combinations,...
Abstract Objective Autoantibody‐mediated forms of encephalitis (AE) include neurological disorders characterized by subacute memory loss, movement disorders, and, often, frequent, focal epileptic seizures. Yet, the electrophysiological effects these autoantibodies on neuronal function have received little attention. In this study, we assessed CSF containing intrinsic and extrinsic properties hippocampal neurons, to define their epileptogenic potential. Methods We compared leucine‐rich glioma...
Choline has been used widely as an agonist for the investigation of gain-of-function mutants nicotinic acetylcholine receptor. It is useful because it behaves like a partial agonist. The efficacy choline difficult to measure blocks channel at concentrations about four times lower than those that activate it. We have fitted activation mechanisms single-channel activity elicited from HEK-expressed human recombinant muscle receptors by and tetramethylammonium (TMA). Channel block was...
The α2 glycine receptor (GlyR) subunit, abundant in embryonic neurons, is replaced by α1 the adult nervous system. single-channel activity of homomeric channels differs from that α1-containing GlyRs, as even at lowest concentration (20 µM), openings occurred long (&gt;300-ms) groups with high open probability (Popen; 0.96; cell-attached recordings, HEK-expressed channels). Shut-time intervals within were dominated short shuttings 5–10 µs. lack dependence suggests they represent single...
Imbalances between excitatory and inhibitory synaptic transmission cause brain network dysfunction are central to the pathogenesis of neurodevelopmental disorders. Parvalbumin interneurons highly implicated in this imbalance. Here, we probed social behavior hippocampal function mice carrying a haploinsufficiency for Ambra1, pro-autophagic gene crucial development. We show that heterozygous Ambra1 (Ambra+/−) characterized by loss parvalbumin interneurons, decreases inhibition/excitation...
Abstract Female, but not male, mice with haploinsufficiency for the proautophagic Ambra1 gene show an autistic-like phenotype associated hippocampal circuits dysfunctions which include loss of parvalbuminergic interneurons (PV-IN), decrease in inhibition/excitation ratio, and abundance immature dendritic spines on CA1 pyramidal neurons. Given paucity data relating to female autism, we exploit +/− model investigate whether rectifying inhibitory input onto principal neurons (PN) rescues their...