A5084162118- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Cholinesterase and Neurodegenerative Diseases
- Classical Antiquity Studies
- Synthesis and Biological Evaluation
- Lipid Membrane Structure and Behavior
- Neuroendocrine regulation and behavior
- Chemical Synthesis and Analysis
- Cellular transport and secretion
- Inorganic and Organometallic Chemistry
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetics and Neurodevelopmental Disorders
- Polyoxometalates: Synthesis and Applications
- Ancient Mediterranean Archaeology and History
- Analytical Chemistry and Sensors
- Autism Spectrum Disorder Research
- Chemical synthesis and alkaloids
- Tryptophan and brain disorders
- Coronary Artery Anomalies
- Synthesis and Reactions of Organic Compounds
- Water Quality Monitoring Technologies
- Wastewater Treatment and Nitrogen Removal
- Pharmacological Receptor Mechanisms and Effects
Film Independent
2022-2024
University of Lausanne
2014-2022
National Research Council
2009-2015
University of Milan
2008-2015
Neuroscience Institute
2011-2015
Istituto di Farmacologia Traslazionale
2011
Istituto Pasteur
1996
Recent studies suggest that the neuronal nicotinic receptors (nAChRs) present in habenulo–interpeduncular (Hb–IPn) system can modulate reinforcing effect of addictive drugs and anxiolytic nicotine. Hb IPn neurons express mRNAs for most nAChR subunits, thus making it difficult to establish subunit composition functional receptors. We used immunoprecipitation immunopurification performed rat wild-type (+/+) β2 knock-out (−/−) mice contain significant β2* β4* populations (each which is...
Astrocytes orchestrate neural development by powerfully coordinating synapse formation and function and, as such, may be critically involved in the pathogenesis of neurodevelopmental abnormalities cognitive deficits commonly observed psychiatric disorders. Here, we report identification a subset cortical astrocytes that are competent for regulating dopamine (DA) homeostasis during postnatal prefrontal cortex (PFC), allowing optimal DA-mediated maturation excitatory circuits. Such control DA...
In astrocytes, the intracellular calcium (Ca2+) signaling mediated by activation of metabotropic glutamate receptor 5 (mGlu5) is crucially involved in modulation many aspects brain physiology, including gliotransmission. Here, we find that mGlu5-mediated Ca2+ leading to release governed mGlu5 interaction with Homer1 scaffolding proteins. We show long splice variants Homer1b/c are expressed astrocytic processes, where they cluster at sites displaying intense local activity. structural and...
α6β2∗ Nicotinic acetylcholine receptors are expressed in selected central nervous system areas, where they involved striatal dopamine (DA) release and its behavioral consequences, other still uncharacterized brain activities. selectively blocked by the α-conotoxins MII PIA, which bear a characteristic N- terminal amino acid tail [arginine (R), aspartic (D), proline (P)]. We synthesized group of PIA-related peptides R1 was mutated or RDP motif gradually removed. Binding DA assays native rat...
Many of the addictive and rewarding effects nicotine are due to its actions on neuronal nicotinic ACh receptor (nAChR) subtypes expressed in dopaminergic mesocorticolimbic cells. The partial agonists, cytisine varenicline, helpful smoking cessation aids. These drugs have a number side that limit their usefulness. aim this study was investigate preclinical pharmacology dimer1,2-bisN-cytisinylethane (CC4).
Despite growing evidence that inhibition of α6β2-containing (α6β2*) nicotinic acetylcholine receptors (nAChRs) may be beneficial for the therapy tobacco addiction, lack good sources α6β2*-nAChRs has delayed discovery α6β2-selective antagonists. Our aim was to generate a cell line stably expressing functional nAChRs with α6β2 properties, enable pharmacological characterization and identification novel antagonists.Different combinations α6, β2, β3, chimeric α6/3 mutant β3(V273S) subunits were...
A set of racemic spirocyclic quinuclidinyl-Δ(2)-isoxazoline derivatives was synthesized using a 1,3-dipolar cycloaddition-based approach. Target compounds were assayed for binding affinity toward rat neuronal homomeric (α7) and heteromeric (α4β2) nicotinic acetylcholine receptors. Δ(2) -Isoxazolines 3 (3-Br), 6 (3-OMe), 5 (3-Ph), 8 (3-OnPr), 4 (3-Me) the ligands with highest α7 subtype (K(i) values equal to 13.5, 14.2, 25.0, 71.6, 96.2 nM, respectively), showed excellent versus α4β2...
Astrocytes are highly secretory cells, participating in rapid brain communication by releasing glutamate. Recent evidences have suggested that this process is largely mediated Ca(2+)-dependent regulated exocytosis of VGLUT-positive vesicles. Here taking advantage VGLUT1-pHluorin and TIRF illumination, we characterized mechanisms glutamate evoked endogenous transmitters (glutamate ATP), which known to stimulate Ca(2+) elevations astrocytes. At first the expressing vesicles found...
A series of unichiral 7-substituted 2-(1'-methyl-2'-pyrrolidinyl)-1,4-benzodioxanes were synthesized and tested for the affinity α4β2 α7 central nicotinic receptors; 2R,2'S diastereomer 7-OH analogue [(R,S)-7], unique in series, has a high (12nM K(i)). N-Demethylation configuration inversion stereocenters greatly weaken its affinity, confirming that such rigid molecule can be considered new template ligands. Docking analysis showed how (R,S)-7 is capable strongly specifically interacting...
Pancreatic β-cells play central roles in blood glucose homeostasis. Beside insulin, these cells release neurotransmitters and other signaling molecules stored synaptic-like microvesicles (SLMVs). We monitored SLMV exocytosis by transfecting a synaptophysin-pHluorin construct visualizing the Total Internal Reflection Fluorescence (TIRF) microscopy. fusion was elicited 20 mM depolarizing K+ concentrations with kinetics comparable to insulin secretion. prevented Tetanus Botulinum-C neurotoxins...
Abstract Epiboxidine hydrochlorides (+)‐ 2 and (−)‐ , which are the structural analogs of antipodes epibatidine (±)‐ 1 as well enantiomeric pairs 3 /(−)‐ 4 were synthesized tested for binding affinity at α4β2 α7 nicotinic acetylcholine receptor (nAChR) subtypes. Final derivatives prepared through condensation racemic N ‐Boc‐7‐azabicyclo[2.2.1]heptane‐2‐one 5 with resolving agent ( R )‐(+)‐2‐methyl‐2‐propanesulfinamide. The pharmacological analysis carried out on three new evidenced an...
Abstract Astrocytes control synaptic activity by modulating peri-synaptic concentrations of ion and neurotransmitters including dopamine and, as such, can be critically involved in the modulation some aspect mammalian behavior. Here we report that genetic mouse model with a reduced medial prefrontal cortex (mPFC) levels, arising from astrocyte-specific conditional deletion vesicular monoamine transporter 2 (VMAT2; aVMTA2cKO mice) shows excessive grooming anxiety-like behaviour. The VMAT2cKO...