A5001895658- Neuroscience and Neuropharmacology Research
- Pain Mechanisms and Treatments
- Photochromic and Fluorescence Chemistry
- Neuropeptides and Animal Physiology
- Photoreceptor and optogenetics research
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurobiology and Insect Physiology Research
- Immunotherapy and Immune Responses
- Receptor Mechanisms and Signaling
- Tryptophan and brain disorders
- Animal testing and alternatives
- Glycosylation and Glycoproteins Research
- Olfactory and Sensory Function Studies
- Genetic Neurodegenerative Diseases
- Cancer, Stress, Anesthesia, and Immune Response
- Amino Acid Enzymes and Metabolism
- Proteoglycans and glycosaminoglycans research
- Mitochondrial Function and Pathology
- Multiple Sclerosis Research Studies
- Pain Management and Opioid Use
- Neurogenesis and neuroplasticity mechanisms
- Cancer therapeutics and mechanisms
- Retinal Development and Disorders
- Sphingolipid Metabolism and Signaling
- Diet and metabolism studies
Istituto Neurologico Mediterraneo
2015-2025
ORCID
2018
University of Molise
2008
Abstract We moved from the hypothesis that perineuronal nets (PNNs), which are condensed structures of extracellular matrix surrounding GABAergic interneurons in forebrain, contribute to mechanisms maladaptive neuronal plasticity underlying chronic pain. Here, we found density PNNs labelled with lectin Wisteria Floribunda Agglutinin (WFA) increased contralateral somatosensory cortex (SSC), medial prefrontal (mPFC), reticular thalamic nucleus (RTN), and insular mice developing neuropathic...
Cinnabarinic acid is an endogenous metabolite of the kynurenine pathway that meets structural requirements to interact with glutamate receptors. We found cinnabarinic acts as a partial agonist type 4 metabotropic (mGlu4) receptors, no activity at other mGlu receptor subtypes. also tested on native mGlu4 receptors by examining 1) inhibition cAMP formation in cultured cerebellar granule cells; 2) protection against excitotoxic neuronal death mixed cultures cortical and 3)...
Abstract Background Spinocerebellar ataxia type 1 (SCA1) is a genetic disorder characterized by severe associated with progressive loss of cerebellar Purkinje cells. The mGlu1 metabotropic glutamate receptor plays key role in mechanisms activity-dependent synaptic plasticity the cerebellum, and its dysfunction linked to pathophysiology motor symptoms SCA1. We used SCA1 heterozygous transgenic mice (Q154/Q2) as model for testing hypothesis that drugs enhance function may be good candidates...
Light-operated drugs constitute a major target in drug discovery, since they may provide spatiotemporal resolution for the treatment of complex diseases (i.e. chronic pain). JF-NP-26 is an inactive photocaged derivative metabotropic glutamate type 5 (mGlu5) receptor negative allosteric modulator raseglurant. Violet light illumination induces photochemical reaction prompting active-drug’s release, which effectively controls mGlu5 activity both ectopic expressing systems and striatal primary...
Pharmacological activation of type-2 metabotropic glutamate receptors (mGlu2 receptors) causes analgesia in experimental models inflammatory and neuropathic pain. Presynaptic mGlu2 are activated by the released from astrocytes means cystine/glutamate antiporter (System x(c)(-) or Sx(c)(-)). We examined analgesic activity Sx(c)(-) activator, N-acetyl-cysteine (NAC), mice developing pain.A single injection NAC (100 mg/kg, i.p.) reduced nocifensive behavior second phase formalin test....
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)...
Background Emerging research seeking novel analgesic drugs focuses on agents targeting group-II metabotropic glutamate receptors (mGlu2 and mGlu3 receptors). N-Acetylcysteine (NAC) enhances the endogenous activation of mGlu2/3 by activating glial glutamate:cystine membrane exchanger. Here, we examined whether NAC inhibits nociceptive responses in humans animals. We tested effect oral (1.2 g) thermal-pain thresholds laser-evoked potentials 10 healthy volunteers, according to a crossover,...
BackgroundL-acetylcarnitine, a drug marketed for the treatment of chronic pain, causes analgesia by epigenetically up-regulating type-2 metabotropic glutamate (mGlu2) receptors in spinal cord. Because epigenetic mechanisms are typically long-lasting, we hypothesized that could outlast duration L-acetylcarnitine models inflammatory and neuropathic pain. ResultsA seven-day with (100 mg/kg, once day, i.p.) produced an antiallodynic effect complete Freund adjuvant mouse model...
Abstract Knowing the site of drug action is important to optimize effectiveness and address any side effects. We used light-sensitive drugs identify brain region-specific role mGlu5 metabotropic glutamate receptors in control pain. Optical activation systemic JF-NP-26, a caged, normally inactive, negative allosteric modulator (NAM) receptors, cingulate, prelimbic infralimbic cortices thalamus inhibited neuropathic pain hypersensitivity. Systemic treatment alloswitch-1, an intrinsically...
N-Acetylcysteine, one of the most prescribed antioxidant drugs, enhances pain threshold in rodents and humans by activating mGlu2 metabotropic glutamate receptors. Here, we assessed analgesic activity N-acetylcysteine streptozotocin model painful diabetic neuropathy examined effect on proteins that are involved mechanisms nociceptive sensitization. Mice with blood glucose levels ≥250 mg/dl response to a single intraperitoneal (i.p.) injection (200 mg/kg) were used for assessment mechanical...
Acid-sensing ion channels (ASICs) are proton-gated involved in multiple biological functions such as: pain modulation, mechanosensation, neurotransmission, and neurodegeneration. Earlier, we described the genetic association, within Nuoro population, between Multiple Sclerosis (MS) rs28936, located ASIC2 3'UTR. Here investigated potential involvement of MS inflammatory process. We induced experimental autoimmune encephalomyelitis (EAE) wild-type (WT), knockout Asic1-/- Asic2-/- mice observed...
Breakthrough cancer pain (BTcP) refers to a sudden and transient exacerbation of pain, which develops in patients treated with opioid analgesics. Fast-onset analgesia is required for the treatment BTcP. Light-activated drugs offer novel potential strategy rapid control without typical adverse effects systemic analgesic drugs. mGlu5 metabotropic glutamate receptor antagonists display potent activity, light-induced activation one these compounds (JF-NP-26) thalamus was found induce models...
Abstract mGlu5 metabotropic glutamate receptors are highly functional in the early postnatal life, and regulate developmental plasticity of parvalbumin-positive (PV + ) interneurons cerebral cortex. PV cells enwrapped by perineuronal nets (PNNs) at closure critical windows cortical plasticity. Changes PNNs have been associated with neurodevelopmental disorders. We found that number Wisteria Fluoribunda Agglutinin (WFA) density WFA /PV were largely increased somatosensory cortex −/− mice...
Cinnabarinic acid (CA) is a trace kynurenine metabolite, which activates both type-4 metabotropic glutamate (mGlu4) and arylic hydrocarbon (Ah) receptors. We examined the action of CA in models inflammatory neuropathic pain moving from evidence that mGlu4 receptors are involved regulation thresholds. Systemic administration low doses (0.125 0.25 mg/kg, i.p.) reduced nocifensive behaviour second phase formalin test. CA-induced analgesia was abrogated receptor knockout mice, but unaffected by...
In cerebellar Purkinje cells (PCs) type-1 metabotropic glutamate (mGlu1) receptors play a key role in motor learning and drive the refinement of synaptic innervation during postnatal development. The cognate mGlu5 receptor is absent mature PCs shows low expression levels adult cortex. Here we found that were heavily expressed by early life, when mGlu1α barely detectable. developmental decline coincided with appearance PCs, both processes associated specular changes CpG methylation...
Experimental animal models are unique tools (i) to study pain transmission and pathophysiology of neuropathic pain, (ii) identify novel molecular targets (iii) test the potential analgesic effect specific molecules. The chronic constriction injury (CCI) model is first post-traumatic painful peripheral neuropathy, originally developed by Bennett Xie in late 1980s. performed sciatic nerve induces a partial denervation involving myelinated afferent axons unmyelinated axons. Damage much more...
Polymorphic variants of the gene encoding for metabotropic glutamate receptor 3 (mGlu3) are linked to schizophrenia. Because abnormalities cortical GABAergic interneurons lie at core pathophysiology schizophrenia, we examined whether mGlu3 receptors influence developmental trajectory transmission in postnatal life. ‐/‐ mice showed robust changes expression interneuron‐related genes prefrontal cortex (PFC), including large reductions parvalbumin (PV) and GluN1 subunit NMDA receptors. The...