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Psycholinguistic studies provide evidence that Italian has more than one basic color term (BCT) for “blue”: consensually, blu denotes “dark blue,” while “light-and-medium blue,” with diatopic variation, is termed either azzurro or celeste. For Tuscan speakers (predominantly from Florence), the BLUE area is argued to linguistically differentiate between azzurro “medium blue” and celeste “light blue.” We scrutinized “basicness” of the three terms. Participants (N = 31; university students/graduates born in Tuscany) named each chip of eight Munsell charts encompassing the BLUE area (5BG-5PB; N = 237) using an unconstrained color-naming method. They then indicated the “best exemplar” (focal color) of blu, azzurro and celeste. We found that frequencies of the three terms and of term derivatives were comparable. Referential meaning of blu, azzurro, and celeste was estimated in CIELAB space as L*a*b*-coordinates of the mean of focal colors and as “modal” categories, that is, dispersion around the mean. The three “blue” terms were distinct on both measures and separated along all three CIELAB dimensions but predominantly along the L*-dimension. Our results provide evidence that Tuscan speakers require all three terms for naming the BLUE area, categorically refined along the lightness dimension. Furthermore, celeste appears to be a third BCT for “blue,” along with commonly considered BCTs azzurro and blu. The “triple blues” as BCTs for Tuscan speakers are in contrast with outcomes of two “blue” basic terms estimated by using the same methodology in two other locations in Italy—azzurro and blu (Verona, Veneto region) or celeste and blu (Alghero, Sardinia).

Cow’s milk allergy (CMA) is one of the earliest and most common food allergy and can be elicited by both IgE- or non-IgE-mediated mechanism. We previously described dysbiosis in children with IgE-mediated CMA and the effect of dietary treatment with extensively hydrolyzed casein formula (EHCF) alone or in combination with the probiotic Lactobacillus rhamnosus GG (LGG). On the contrary, the gut microbiota in non-IgE-mediated CMA remains uncharacterized. In this study we evaluated gut microbiota composition and fecal butyrate levels in children affected by non-IgE-mediated CMA. We found a gut microbiota dysbiosis in non-IgE-mediated CMA, driven by an enrichment of Bacteroides and Alistipes . Comparing these results with those previously obtained in children with IgE-mediated CMA, we demonstrated overlapping signatures in the gut microbiota dysbiosis of non-IgE-mediated and IgE-mediated CMA children, characterized by a progressive increase in Bacteroides from healthy to IgE-mediated CMA patients. EHCF containg LGG was more strongly associated with an effect on dysbiosis and on butyrate production if compared to what observed in children treated with EHCF alone. If longitudinal cohort studies in children with CMA will confirm these results, gut microbiota dysbiosis could be a relevant target for innovative therapeutic strategies in children with non-IgE-mediated CMA.

Epigenetic mechanisms, such as alterations in histone acetylation based on histone deacetylases (HDACs) activity, have been linked not only to normal brain function but also to several brain disorders including epilepsy and the epileptogenic process. In WAG/Rij rats, a genetic model of absence epilepsy, epileptogenesis and mild-depression comorbidity, we investigated the effects of two HDAC inhibitors (HDACi), namely sodium butyrate (NaB), valproic acid (VPA) and their co-administration, on the development of absence seizures and related psychiatric/neurologic comorbidities following two different experimental paradigms. Treatment effects have been evaluated by EEG recordings (EEG) and behavioural tests at different time points. Prolonged and daily VPA and NaB treatment, started before absence seizure onset (P30), significantly reduced the development of absence epilepsy showing antiepileptogenic effects. These effects were enhanced by NaB/VPA co-administration. Furthermore, early-chronic HDACi treatment improved depressive-like behaviour and cognitive performance 1 month after treatment withdrawal. WAG/Rij rats of 7 months of age showed reduced acetylated levels of histone H3 and H4, analysed by Western Blotting of homogenized brain, in comparison to WAG/Rij before seizure onset (P30). The brain histone acetylation increased significantly during treatment with NaB or VPA alone and more markedly during co-administration. We also observed decreased expression of both HDAC1 and 3 following HDACi treatment compared to control group. Our results suggest that histone modifications may have a crucial role in the development of epilepsy and early treatment with HDACi might be a possible strategy for preventing epileptogenesis also affecting behavioural comorbidities.

Background: Transient Receptor Potential Melastatin-8 (TRPM8) is a non-selective cation channel activated by cold temperature and by cooling agents. Several studies have proved that this channel is involved in pain perception. Although some studies indicate that TRPM8 inhibition is necessary to reduce acute and chronic pain, it is also reported that TRPM8 activation produces analgesia. These conflicting results could be explained by extracellular Ca2+-dependent desensitization that is induced by an excessive activation. Likely, this effect is due to phosphatidylinositol 4,5-bisphosphate (PIP2) depletion that leads to modification of TRPM8 channel activity, shifting voltage dependence towards more positive potentials. This phenomenon needs further evaluation and confirmation that would allow us to understand better the role of this channel and to develop new therapeutic strategies for controlling pain. Experimental approach: To understand the role of TRPM8 in pain perception, we tested two specific TRPM8-modulating compounds, an antagonist (IGM-18) and an agonist (IGM-5), in either acute or chronic animal pain models using male Sprague-Dawley rats or CD1 mice, after systemic or topical routes of administration. Results: IGM-18 and IGM-5 were fully characterized in vivo. The wet-dog shake test and the body temperature measurements highlighted the antagonist activity of IGM-18 on TRPM8 channels. Moreover, IGM-18 exerted an analgesic effect on formalin-induced orofacial pain and chronic constriction injury-induced neuropathic pain, demonstrating the involvement of TRPM8 channels in these two pain models. Finally, the results were consistent with TRPM8 downregulation by agonist IGM-5, due to its excessive activation. Conclusions: TRPM8 channels are strongly involved in pain modulation, and their selective antagonist is able to reduce both acute and chronic pain.

An increasing number of studies in recent years have focused on the role that the gut may play in Parkinson’s Disease (PD) pathogenesis, suggesting that the maintenance of a healthy gut may lead to potential treatments of the disease. The health of microbiota has been shown to be directly associated with parameters that play a potential role in PD including gut barrier integrity, immunity, function, metabolism and the correct functioning of the gut-brain axis. The gut microbiota (GM) may therefore be employed as valuable indicators for early diagnosis of PD and potential targets for preventing or treating PD symptoms. Preserving the gut homeostasis using probiotics may therefore lead to a promising treatment strategy due to their known benefits in improving constipation, motor impairments, inflammation, and neurodegeneration. However, the mechanisms underlying the effects of probiotics in PD are yet to be clarified. In this project, we have tested the efficacy of an oral probiotic suspension, Symprove™, on an established animal model of PD. Symprove™, unlike many commercially available probiotics, has been shown to be resistant to gastric acidity, improve symptoms in gastrointestinal diseases and improve gut integrity in an in vitro PD model. In this study, we used an early-stage PD rat model to determine the effect of Symprove™ on neurodegeneration and neuroinflammation in the brain and on plasma cytokine levels, GM composition and short chain fatty acid (SCFA) release. Symprove™ was shown to significantly influence both the gut and brain of the PD model. It preserved the gut integrity in the PD model, reduced plasma inflammatory markers and changed microbiota composition. The treatment also prevented the reduction in SCFAs and striatal inflammation and prevented tyrosine hydroxylase (TH)-positive cell loss by 17% compared to that observed in animals treated with placebo. We conclude that Symprove™ treatment may have a positive influence on the symptomology of early-stage PD with obvious implications for the improvement of gut integrity and possibly delaying/preventing the onset of neuroinflammation and neurodegeneration in human PD patients.

  N-acetylcysteine (NAC) is an antioxidant with some demonstrated efficacy in a range of neuropsychiatric disorders. NAC has shown anticonvulsant effects in animal models. NAC effects on absence seizures are still not uncovered, and considering its clinical use as a mucolytic in patients with lung diseases, people with epilepsy are also likely to be exposed to the drug. Therefore, we aimed to study the effects of NAC on absence seizures in the WAG/Rij rat model of absence epilepsy with neuropsychiatric comorbidities. The effects of NAC chronic treatment in WAG/Rij rats were evaluated on: absence seizures at 15 and 30 days by EEG recordings and animal behaviour at 30 days on neuropsychiatric comorbidities. Furthermore, the mechanism of action of NAC was evaluated by analysing brain expression levels of some possible key targets: the excitatory amino acid transporter 2, cystine–glutamate antiporter, metabotropic glutamate receptor 2, the mechanistic target of rapamycin and p70S6K as well as levels of total glutathione. Our results demonstrate that in WAG/Rij rats, NAC treatment significantly increased the number and duration of SWDs, aggravating absence epilepsy while ameliorating neuropsychiatric comorbidities. NAC treatment was linked to an increase in brain mGlu2 receptor expression with this being likely responsible for the observed absence seizure-promoting effects. In conclusion, while confirming the positive effects on animal behaviour induced by NAC also in epileptic animals, we report the aggravating effects of NAC on absence seizures which could have some serious consequences for epilepsy patients with the possible wider use of NAC in clinical therapeutics.

BackgroundThe current COVID-19 pandemic has abruptly catalysed a shift towards remote assessment in neuropsychological practice (tele-neuropsychology, t-NPs). Although the validity of t-NPs diagnostics is gaining recognition worldwide, little is known about its implementation in Italy. The present review by the Italian working group on tele-neuropsychology (TELA) aims at describing the availability, psychometric properties, and feasibility of t-NPs tools currently available in Italy.MethodsPreferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. This work was pre-registered on the Prospective Register of Systematic Reviews (PROSPERO; CRD42021239687). Observational studies reporting telephone-, videoconference- or web-based assessment of cognition/behaviour in Italian both healthy participants (HPs) and patients were included. Bias assessment was performed through ad hoc scales.ResultsFourteen studies were included from an initial N = 895 (4 databases searched). Studies were subdivided into those focused on psychometric properties and those characterized by a predominant applied nature. The majority of studies addressed either adult/elderly HPs or neurological/internal patients. Multi-domain screening tools for cognition, behaviour, mood/anxiety and quality of life were the most represented. Findings regarding validity, reliability, sensitivity, specificity and clinical usability were reported for cognitive screenings — the telephone- and videoconference-based Mini-Mental State Examination and the Telephone Interview for Cognitive Status.DiscussionPositive albeit preliminary evidence regarding psychometric properties and feasibility in both clinical and non-clinical populations of Italian t-NPs brief screening tools are herewith provided. Further studies exploring clinical usability of t-NPs and psychometric properties/feasibility of tests for the in-depth assessment of specific cognitive domains are necessary.

Obesity is a health concern worldwide, and its onset is multifactorial. In addition to metabolic syndrome, a high-fat diet induces many deleterious downstream effects, such as chronic systemic inflammation, a loss of gut barrier integrity, and gut microbial dysbiosis, with a reduction of many butyrate-producing bacteria. These conditions can be ameliorated by increasing legumes in the daily diet. White and kidney beans ( Phaseolus vulgaris L.) and their non-nutritive bioactive component phaseolamin were demonstrated to mitigate several pathological features related to a metabolic syndrome-like condition. The aim of the present study was to investigate the molecular pathways involved in the protective effects on the intestinal and liver environment of a chronic oral treatment with P. vulgaris extract (PHAS) on a murine model of the high-fat diet. Results show that PHAS treatment has an anti-inflammatory effect on the liver, colon, and cecum. This protective effect was mediated by peroxisome proliferator-activated receptor (PPAR)-α and γ. Moreover, we also observed that repeated PHAS treatment was able to restore tight junctions’ expression and protective factors of colon and cecum integrity disrupted in HFD mice. This improvement was correlated with a significant increase of butyrate levels in serum and fecal samples compared to the HFD group. These data underline that prolonged treatment with PHAS significantly reduces some pathological features related to the metabolic syndrome-like condition, such as inflammation and intestinal barrier disruption; therefore, PHAS could be a valid tool to be associated with the therapeutic strategy.

Pain conditions, such as neuropathic pain (NP) and persistent inflammatory pain are therapeutically difficult to manage. Previous studies have shown the involvement of glutamate receptor in pain modulation and in particular same of these showed the key role of the AMPA ionotropic glutamate receptor subtype. Antiseizure medications (ASMs) are often used to treat this symptom, however the effect of perampanel (PER), an ASM acting as selective, non-competitive inhibitor of the AMPA receptor on the management of pain has not well been investigated yet. Here we tested the potential analgesic and anti-inflammatory effects of PER, in acute and chronic pain models. PER was given orally either in acute (5 mg/kg) or repeated administration (3 mg/kg/d for 4 days). Pain response was assessed using models of nociceptive sensitivity, visceral and inflammatory pain, and mechanical allodynia and hyperalgesia induced by chronic constriction injury to the sciatic nerve. PER significantly reduced pain perception in all behavioral tests as well as CCI-induced mechanical allodynia and hyperalgesia in acute regimen (5 mg/kg). This effect was also observed after repeated treatment using the dose of 3 mg/kg/d. The antinociceptive, antiallodynic and antihyperalgesic effects of PER were attenuated when the CB 1 antagonist AM251 (1 mg/kg/i.p.) was administered before PER treatment, suggesting the involvement of the cannabinergic system. Moreover, Ex vivo analyses showed that PER significantly increased CB 1 receptor expression and reduced inflammatory cytokines (i.e. TNFα, IL-1β, and IL-6) in the spinal cord. In conclusion, these results extend our knowledge on PER antinociceptive and antiallodynic effects and support the involvement of cannabinergic system on its mode of action.

Epilepsy is a common neurological disease characterized by the enduring predisposition of the brain to generate seizures. Among the recognized causes, a role played by the gut microbiota in epilepsy has been hypothesized and supported by new investigative approaches. To dissect the microbiota‐gut‐brain (MGB) axis involvement in epilepsy, in vitro modeling approaches arouse interest among researchers in the field. This review summarizes, first of all, the evidence of a role of the MGB axis in epilepsy by providing an overview of the recent clinical and preclinical studies and showing how dietary modification, microbiome supplementations, and hence, microbiota alterations may have an impact on seizures. Subsequently, the currently available strategies to study epilepsy on animal and in vitro models are described, focusing attention on these latter and the technological challenges for integration with already existing MGB axis models. Finally, the implementation of existing epilepsy in vitro systems is discussed, offering a complete overview of the available technological tools which may improve reliability and clinical translation of the results towards the development of innovative therapeutic approaches, taking advantage of complementary technologies.