A5064196678- Nicotinic Acetylcholine Receptors Study
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Neuroscience and Neural Engineering
- Photoreceptor and optogenetics research
- Adenosine and Purinergic Signaling
- Epilepsy research and treatment
- Genetic Neurodegenerative Diseases
- Advanced Memory and Neural Computing
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetics and Neurodevelopmental Disorders
- Nerve injury and regeneration
- Nanowire Synthesis and Applications
- Endoplasmic Reticulum Stress and Disease
- Cholinesterase and Neurodegenerative Diseases
- Pain Mechanisms and Treatments
- Synthesis and Biological Evaluation
- Myasthenia Gravis and Thymoma
- Cardiac electrophysiology and arrhythmias
- Neural dynamics and brain function
- Parkinson's Disease Mechanisms and Treatments
- Tissue Engineering and Regenerative Medicine
- Mitochondrial Function and Pathology
- Pharmacological Receptor Mechanisms and Effects
Istituto Neurologico Mediterraneo
2016-2025
Sapienza University of Rome
2016-2025
Istituto Pasteur
2003-2020
Institute of Biomedical Technologies
2015
University of Pavia
2015
National Research Council
2015
University of Colorado Boulder
2015
Foundation University Islamabad
2012
Institut Pasteur
1999-2006
Istituto di Istruzione Superiore I.T.C. Di Vittorio
2006
Abstract The mechanisms of communication between the brain and immune cells are still largely unclear. Here, we characterize populations resident natural killer (NK) innate lymphoid (ILC) 1 in meningeal dura layer adult mice. We describe that ILC1/NK cell-derived interferon-γ acetylcholine can contribute to modulation homeostatic functions, shaping synaptic neuronal transmission neurotransmitter levels with effects on mice behavior. In detail, plays a role formation non-spatial memory,...
Huntington disease (HD) is a genetic neurodegenerative disorder for which there currently no cure and way to stop or even slow the brain changes it causes. In present study, we aimed investigate whether FTY720, first approved oral therapy multiple sclerosis, may be effective in HD models eventually constitute an alternative therapeutic approach treatment of disease. Here, utilized preclinical target validation paradigms examined vivo efficacy chronic administration FTY720 R6/2 mouse model....
Summary Purpose The chemokine fractalkine/ CX 3 CL 1 and its receptor CR are widely expressed in the central nervous system ( CNS ). Recent evidence showed that participates inflammatory responses common features of disorders, such as epilepsy. Mesial temporal lobe epilepsy MTLE ) is prevalent form focal adults, hippocampal sclerosis HS represents most underlying pathologic abnormality, demonstrated at autopsy postresection studies. Relevant a characteristic pattern neuronal loss,...
Rationale: Long living individuals show delay of aging, which is characterized by the progressive loss cardiovascular homeostasis, along with reduced endothelial nitric oxide synthase activity, dysfunction, and impairment tissue repair after ischemic injury. Objective: Exploit genetic analysis long to reveal master molecular regulators physiological aging new targets for treatment disease. Methods Results: We that polymorphic variant rs2070325 (Ile229Val) in...
Extracellular adenosine, a key regulator of neuronal excitability, is metabolized by astrocyte-based enzyme adenosine kinase (ADK).We hypothesized that ADK might be an upstream adenosine-based homeostatic brain functions simultaneously affecting several downstream pathways.We therefore studied the relationship between expression, levels extracellular synaptic transmission, intrinsic and brain-derived neurotrophic factor (BDNF)-dependent actions in transgenic mice underexpressing or...
Parkinson's disease (PD) represents the most common neurodegenerative movement disorder. We recently identified 16 novel genes associated with PD. In this study, we focused attention on and rare variants in lysosomal K+ channel TMEM175. The study includes a detailed clinical genetic analysis of 400 cases 300 controls. Molecular studies were performed patient-derived fibroblasts. functional properties mutant channels assessed by patch-clamp technique co-immunoprecipitation. have found that...
Pathogenic variants in the
Abstract Heteromeric nicotinic acetylcholine nAChRs (nAChRs) containing the α4 and β2 subunits (α4β2 * nAChRs) modulate neurotransmitter release in several regions of brain. In temporal lobe epilepsy, inhibitory GABAergic neurotransmission is altered, whereas no evidence dysfunction has been reported. Here, we investigated, human epileptic cortical tissues, ability α4β2 to synaptic transmission. An increased expression was observed cortex patients. We then recorded excitatory postsynaptic...
A study was made of the "rundown" GABA(A) receptors, microtransplanted to Xenopus oocytes from surgically resected brain tissues patients afflicted with drug-resistant human mesial temporal lobe epilepsy (mTLE). Cell membranes, isolated mTLE neocortex specimens, were injected into frog that rapidly incorporated functional receptors. Upon repetitive activation GABA (1 mM), "epileptic" receptors exhibited a GABA(A)-current (I(GABA)) rundown significantly enhanced by Zn(2+) (</=250 microM), and...
Neuronal nicotinic acetylcholine receptors (nAChRs) containing the α5 subunit modulate nicotine consumption, and human CHRNA5 rs16969968 polymorphism, causing replacement of aspartic acid residue at position 398 with an asparagine (α5DN), has recently been associated increased use tobacco higher incidence lung cancer. We show that in ventral midbrain neurons, is essential for heteromeric nAChR-induced intracellular-free Ca(2+) concentration elevations α5(-/-) mice, a class large-amplitude...
Mutations in SCN1A gene, encoding the voltage-gated sodium channel (VGSC) NaV1.1, are widely recognized as a leading cause of genetic febrile seizures (FS), due to decrease Na+ current density, mainly affecting inhibitory neuronal transmission. Here, we generated induced pluripotent stem cells (iPSCs)-derived neurons (idNs) from patient belonging genetically well-characterized Italian family, carrying c.434T > C mutation gene (hereafter SCN1AM145T). A side-by-side comparison diseased and...
Chronic pain is sustained by a maladaptive form of neuronal plasticity occurring in all stations the neuraxis, including cortical regions matrix. We report that chronic inflammatory induced unilateral injection complete Freund's adjuvant (CFA) hindpaw male mice was associated with progressive build-up perineuronal nets (PNNs) contralateral somatosensory cortex (SSC), medial prefrontal (mPFC), and reticular thalamic nucleus. In SSC, density PNNs labeled Wisteria floribunda agglutinin (WFA)...
Cyclothiazide (CTZ), a positive allosteric modulator of ionotropic α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors, is used frequently to block the desensitization both native and heterologously expressed AMPA receptors. Specifically, CTZ known produce fast inhibition receptor much slower potentiation current. By using patch-clamp techniques, effects were studied in HEK 293 cells stably transfected with rat flip GluR1 subunit. Upon treatment, we found an...
Refractory temporal lobe epilepsy (TLE) is associated with a dysfunction of inhibitory signaling mediated by GABA A receptors. In particular, the use-dependent decrease (run-down) currents (I ) evoked repetitive activation receptors markedly enhanced in hippocampal and cortical neurons TLE patients. Understanding role I run-down disease, its mechanisms, may allow development medical alternatives to surgical resection, but such mechanistic insights are difficult pursue human tissue....
Sporadic amyotrophic lateral sclerosis (SALS) is a motor neuron degenerative disease of unknown etiology. Current thinking on SALS that multiple genetic and environmental factors contribute to liability. Since neuronal acetylcholine receptors (nAChRs) are part the glutamatergic pathway, we searched for sequence variants in CHRNA3, CHRNA4 CHRNB4 genes, encoding nicotinic AChR subunits, 245 patients 450 controls. We characterized missense by vitro mutagenesis, cell transfection...
AimsThe lipid and protein kinase phosphoinositide 3-kinase γ (PI3Kγ) is abundantly expressed in inflammatory cells the cardiovascular tissue. In recent years, its role inflammation cardiac function remodelling has been unravelled, highlighting beneficial effects of pharmacological inhibition. Furthermore, a for PI3Kγ regulation vascular tone emphasized. However, impact this signalling control blood pressure still poorly understood. Our study investigated effect selective inhibition PI3Kγ,...
Glioma is the most common and primary brain tumors in adults. Despite available multimodal therapies, glioma patients appear to have a poor prognosis. The Hedgehog (Hh) signaling involved tumorigenesis emerged as promising target for tumors. Glabrescione B (GlaB) has been recently identified first direct inhibitor of Gli1, downstream effector pathway. We established overexpression Gli1 murine cells (GL261) GlaB effect on cell viability. used 1H-nuclear magnetic resonance (NMR) metabolomic...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no effective therapy, causing progressive loss of motor neurons in the spinal cord, brainstem, and cortex. Regardless its genetic or sporadic origin, there currently cure for ALS therapy that can reverse control progression. In present study, taking advantage human superoxide dismutase-1 mutant (hSOD1-G93A) mouse recapitulates key pathological features ALS, we investigated possible role voltage-gated potassium...
Abstract We examine some of the biological and physiological properties avian α 6 neuronal nicotinic acetylcholine receptor (nAChR) subunit. show here that, beginning at embryonic day 5, mRNA is abundantly expressed in developing chick neuroretina, where it coexists with other subunit mRNAs such as 3 , β 2 4 . In contrast, absent from optic tectum peripheral ganglia. Despite numerous efforts, has long failed critical test functional reconstitution. Here we use patch‐clamp techniques confocal...
Combinations of cDNAs encoding mouse and chick nicotinic acetylcholine receptor (nAChR) subunits were transiently transfected into human BOSC 23 cells, the expressed receptors studied by simultaneously recording transmembrane currents fluorescence transients using whole‐cell patch‐clamp technique, confocal microscopy with Ca 2+ indicator dye fluo‐3. The fractional current, P f , nAChRs was evaluated as normalized ratio nicotine‐evoked transient over total charge entering cell ( F / Q ratio)....