Biology subjects

Nicoletti, F.

Publications and source records attributed to Nicoletti, F..

3 recordsLinked to original sources

bioRxiv2026

Diagnostic Value of Antibody Responses to Mycobacterium avium subsp. paratuberculosis-Derived Proteins PtpA and PtpB in Rheumatoid Arthritis

Evidence suggests that Mycobacterium avium subspecies paratuberculosis (MAP) may contribute to autoimmune diseases such as rheumatoid arthritis (RA), partly through effector proteins--particularly the tyrosine phosphatases PtpA and PtpB--that modulate macrophage signaling and promote bacterial persistence. This study evaluated whether serum antibodies against these proteins serve as biomarkers of RA. Humoral responses to PtpA and PtpB were quantified in Mexican RA patients (n = 100) and healthy controls (n = 100) using in-house ELISAs. Associations with disease activity (DAS28), ROC performance, and logistic regression models were assessed. Results showed that anti-PtpB antibody levels were significantly higher in patients with RA than in healthy controls (median OD 0.185 vs. 0.080; p < 0.0001) and had moderate discriminative capacity (AUC = 0.762). Anti-PtpB reactivity increased with higher disease activity and showed a significant positive association with DAS28 (p < 0.05). In addition, there was a functional disability measured by HAQ (p < 0.001), as well as moderate correlations with erythrocyte sedimentation rate and rheumatoid factor. A combined logistic regression model integrating both antibodies markedly improved diagnostic accuracy (AUC = 0.934), achieving high sensitivity (90%) and specificity (89%). These findings support a potential role of MAP in RA immunopathogenesis and indicate that combined quantification of anti-PtpA and anti-PtpB antibodies captures complementary and non-redundant immunological information. This combined serological approach may enhance RA diagnosis and provide clinically relevant insights into disease activity and severity.

microbiology↗

bioRxiv2024

A 'double-edged' role for type-5 metabotropic glutamate receptors in pain disclosed by light-sensitive drugs

Knowing the site of drug action is important to optimize effectiveness and address any side effects. We used light-sensitive drugs to identify the brain region-specific role of mGlu5 metabotropic glutamate receptors in the control of pain. Optical activation of systemic JF-NP-26, a caged, normally inactive, negative allosteric modulator (NAM) of mGlu5 receptors, in cingulate, prelimbic and infralimbic cortices and thalamus inhibited neuropathic pain hypersensitivity. Systemic treatment of alloswitch-1, an intrinsically active mGlu5 receptor NAM, caused analgesia, and the effect was reversed by light-induced drug inactivation in in the prelimbic and infralimbic cortices, and thalamus. This demonstrates that mGlu5 receptor blockade in the medial prefrontal cortex and thalamus is both sufficient and necessary for the analgesic activity of mGlu5 receptor antagonists. Surprisingly, when light was delivered in the basolateral amygdala, local activation of systemic JF-NP-26 reduced pain thresholds, whereas inactivation of alloswitch-1 enhanced analgesia. Electrophysiological analysis showed that alloswitch-1 increased excitatory synaptic responses in prelimbic pyramidal neurons evoked by stimulation of BLA input, and decreased feedforward inhibition of amygdala output neurons by BLA. Both effects were reversed by optical silencing and reinstated by optical reactivation of alloswitch-1. These findings demonstrate for the first time that the action of mGlu5 receptors in the pain neuraxis is not homogenous, and suggest that blockade of mGlu5 receptors in the BLA may limit the overall analgesic activity of mGlu5 receptor antagonists. This could explain the suboptimal effect of mGlu5 NAMs on pain in human studies and validate photopharmacology as an important tool to determine ideal target sites for systemic drugs.

neuroscience↗

bioRxiv2020

Activating mGlu3 metabotropic glutamate receptors rescues schizophrenia-like cognitive deficits through metaplastic adaptations within the hippocampus.

BackgroundPolymorphisms in GRM3, the gene encoding the mGlu3 metabotropic glutamate receptor, are associated with impaired cognition and neuropsychiatric disorders such as schizophrenia. Limited availability of selective genetic and molecular tools has hindered progress in developing a clear understanding of the mechanisms through which mGlu3 receptors regulate synaptic plasticity and cognition. MethodsWe examined associative learning in mice with trace fear conditioning, a hippocampal-dependent learning task disrupted in patients with schizophrenia. Underlying cellular mechanisms were assessed using ex vivo hippocampal slice preparations with selective pharmacological tools and selective genetic deletion of mGlu3 receptor expression in specific neuronal subpopulations. ResultsmGlu3 receptor activation enhanced trace fear conditioning and reversed deficits induced by subchronic phencyclidine. Mechanistic studies revealed that mGlu3 receptor activation induced metaplastic changes, biasing afferent stimulation to induce long-term potentiation through a mGlu5 receptor-dependent, endocannabinoid-mediated, disinhibitory mechanism. Selective genetic deletion of either mGlu3 or mGlu5 from hippocampal pyramidal cells eliminated effects of mGlu3 activation, revealing a novel mechanism by which mGlu3 and mGlu5 interact to enhance cognitive function. ConclusionsThese data demonstrate that activation of mGlu3 receptors in hippocampal pyramidal cells enhances hippocampal-dependent cognition in control and impaired mice by inducing a novel form of metaplasticity to regulate circuit function - providing a clear mechanism through which genetic variation in GRM3 can contribute to cognitive deficits. Developing approaches to positively modulate mGlu3 receptor function represents an encouraging new avenue for treating cognitive disruption in schizophrenia and other psychiatric diseases.

pharmacology and toxicology↗