A5090548570- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Stress Responses and Cortisol
- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Neuroendocrine regulation and behavior
- Anesthesia and Neurotoxicity Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Memory and Neural Mechanisms
- Tryptophan and brain disorders
- Molecular Sensors and Ion Detection
- Nicotinic Acetylcholine Receptors Study
- Biochemical effects in animals
- Anesthesia and Sedative Agents
- Adipose Tissue and Metabolism
- Medicinal Plants and Neuroprotection
- Cannabis and Cannabinoid Research
- GABA and Rice Research
- Phytochemicals and Medicinal Plants
- Photochromic and Fluorescence Chemistry
- Biochemical Analysis and Sensing Techniques
- Neurogenesis and neuroplasticity mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Analytical Methods in Pharmaceuticals
- Neural dynamics and brain function
University of Cagliari
2014-2024
Neuroscience Institute
2003-2024
National Research Council
2013-2024
Scripps Research Institute
2024
Istituto Nazionale di Fisica Nucleare, Sezione di Cagliari
2003-2024
National Academies of Sciences, Engineering, and Medicine
2014-2023
TU Dresden
2013
University of Freiburg
2013
Institute of High Performance Computing
2013
University of Stuttgart
2013
An interaction with the GABA type A (GABA ) receptor has long been recognized as one of main neurochemical mechanisms underlying many pharmacological actions ethanol. However, more recent data have suggested that certain behavioral and electrophysiological ethanol are mediated by an increase in brain concentration neuroactive steroids results from stimulation hypothalamic-pituitary-adrenal (HPA) axis. Neuroactive such 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP) are, fact, potent efficacious...
The effect of long‐term treatment with ethanol was investigated on the function γ ‐aminobutyric acid A (GABA ) and N ‐methyl‐d‐as‐partic (NMDA) receptors. Rats were rendered ethanol‐dependent by repeated forced administration a 20% solution (12 to 18 g/kg/day po) for 6 days tested while still intoxicated or at different time intervals after withdrawal. t ‐[ 36 S]Butylbicyclophosphorothionate ( 35 S‐TBPS) binding increased 30% in cortical homogenates rats killed 1 3 hr last administration,...
The intravenous general anesthetic 2,6-diisopropylphenol (propofol) potentiates GABAA receptor function, but the precise mechanisms and specificity of this action are still unclear. To study influence subunit composition on propofol, 18 different combinations cloned cDNAs coding for human brain isoforms receptor, as well mRNAs from mouse brain, were expressed in Xenopus oocytes, effects investigated by voltage-clamp technique. We found that low concentrations (1-10 microM) propofol...
Abstract: The effect of the general anesthetic propofol on t‐ [ 35 S]butylbicyclophosphorothionate ([ S]TBPS) binding to unwashed membrane preparations from rat cerebral cortex was studied and compared that other anesthetics (pentobarbital, alphaxalone) which are known enhance GABAergic transmission. Propofol produced a concentration‐dependent complete inhibition S]TBPS binding, an similar induced by pentobarbital alphaxalone, although these agents differ markedly in potency (alphaxalone...
Alcoholism involves long-term cognitive deficits, including memory impairment, resulting in substantial cost to society. Neuronal refinement and stabilization are hypothesized confer resilience poor decision making addictive-like behaviors, such as excessive ethanol drinking dependence. Accordingly, structural abnormalities likely contribute synaptic dysfunctions that occur from suddenly ceasing the use of alcohol after chronic ingestion. Here we show ethanol-dependent rats display a loss...
Background: The loss of nigrostriatal neurons containing dopamine (DA) together with the “mitochondrial dysfunction” in midbrain represent two main causes related to symptoms Parkinson’s disease (PD). Hence, aim this investigation is co-administer missing DA and antioxidant grape seed-derived proanthocyanidins (grape seed extract, GSE) order increase levels neurotransmitter (which unable cross Blood Brain Barrier) reducing oxidative stress (OS) PD, respectively. Methods: For purpose, we...
Changes in the expression of subunits GABA type A (GABA<sub>A</sub>) receptor are implicated development ethanol tolerance and dependence as well central hyperexcitability associated with withdrawal. The impact such changes on GABA<sub>A</sub> function pharmacological sensitivity was investigated cultured rat hippocampal neurons exposed to for 5 d then subjected Both treatment withdrawal were a marked decrease maximal density GABA-evoked Cl<sup>-</sup> currents, whereas potency unaffected....
In this study we determined the influence of gamma-aminobutyric acid (GABA)A receptor subunit composition on direct effects general anesthetics propofol, pentobarbital, and alphaxalone, using recombinant receptors expressed in Xenopus oocytes. cDNAs coding for human beta 1, alpha 1 or gamma 2S GABAA subunits were injected into oocytes, responses induced by either GABA measured two-electrode voltage-clamp recording. Expression homomeric resulted formation a Cl- channel that was sensitive to...
The substituent effects at positions 6 and 8 (compounds 17−31) as well the amide nitrogen 32−40) of a series 2-phenylimidazo[1,2-a]pyridineacetamides were evaluated both central (CBR) peripheral (PBR) benzodiazepine receptors. structure−activity relationship studies detailed herein indicate key structural features required for high affinity selectivity PBR. Substitution on imidazopyridine nucleus position with lipophilic substituents presence one chlorine atom para phenyl ring C(2) are...
A number of 6-substituted or 6,8-disubstituted alkyl 2-phenylimidazo[1,2-alpha]pyridine-3-carboxylates 5a-h, -acetates 5i-s, 6a-g, and -propionates 5t, 6h N,N-dialkyl-2-phenylimidazo[1,2-alpha]pyridine-3-carboxamides 7a-d,-acetamides 7e-t -propionamide 7u were prepared following new synthetic methods, their affinities for both the central (CBR) peripheral (PBR) benzodiazepine receptors evaluated. The compounds ester series displayed low affinity receptor types. Conversely, most...
Selective activation of peripheral benzodiazepine receptors (PBRs) in adrenal cells and brain oligodendrocytes promotes steroidogenesis. Three 2-phenyl-imidazo[1,2-a]pyridine derivatives (CB 34, CB 50 54) have now been investigated with regard to their selectivity for PBRs ability stimulate central steroidogenesis rats. The three compounds (10(-10)-10(-4) M) potently inhibited the binding PBR ligand [3H]-PK 11195 ovary membranes vitro, without substantially affecting [3H]-flunitrazepam...
A series of imidazopyridine acetamides were synthesized to evaluate the effects structural changes at both central (CBRs) and peripheral benzodiazepine receptors (PBRs). These include introduction polar substituents or ionizable functional groups 2- 8-position skeleton. The results suggest that endowed with hydrogen bonding acceptor and/or donor properties in para position phenyl ring lead high affinity for PBR. In electrophysiological studies, it was found compounds 9, 12, 13, 28 markedly...
Pregnancy is associated with changes in mood and anxiety level as well marked hormonal fluctuations. Increases the brain concentrations of neuroactive steroids during pregnancy rats are accompanied by expression subunits GABA type A receptor (GABA -R) brain. Granule cells dentate gyrus (DGGCs) exhibit two components inhibitory GABAergic transmission: a phasic component mediated synaptic -Rs, tonic extrasynaptic -Rs. Recordings currents were obtained from hippocampal slices prepared estrus,...
A number of propofol (2,6-diisopropylphenol) congeners and derivatives were synthesized their in vitro capability to affect GABAA receptors determined by the inhibition specific [35S]-tert-butylbicyclophosphorothionate ([35S]TBPS) binding rat whole brain membranes. Introduction halogen (Cl, Br, I) benzoyl substituents para position phenyl group resulted ligands with higher potency at inhibiting [35S]TBPS binding. quantitative structure−affinity relationship (QSAR) study demonstrated that...