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Background: Autism spectrum disorder (ASD) diagnoses have rapidly increased globally. Both environmental and genetic factors appear to contribute to the development of ASD. Several studies have shown a potential association between prenatal or postnatal pesticide exposure and the risk of developing ASD. Methods: We reviewed the available literature concerning the relationship between early life exposure to pesticides used in agriculture, such as organochlorines, organophosphates and pyrethroids, and ASD onset in childhood. We searched on Medline and Scopus for cohort or case–control studies published in English from 1977 to 2020. Results: A total of seven articles were selected for the review. We found a remarkable association between the maternal exposure to pyrethroid, as well as the exposure to organophosphate during pregnancy or in the first years of childhood, and the risk of ASD onset. This association was found to be less evident with organochlorine pesticides. Pregnancy seems to be the time when pesticide exposure appears to have the greatest impact on the onset of ASD in children. Conclusions: Among the different environmental pollutants, pesticides should be considered as emerging risk factors for ASD. The potential association identified between the exposure to pesticides and ASD needs to be implemented and confirmed by further epidemiological studies based on individual assessment both in outdoor and indoor conditions, including multiple confounding factors, and using statistical models that take into account single and multiple pesticide residues.

Among therapeutic approaches that have been investigated, targeting of receptors implicated in managing neuroinflammation has been described. One such family of receptors comprises the formyl peptide receptors (FPRs) whose ligands could play a role in host defense. The murine FPR gene family includes at least six members while in humans there are only three. The two most important members are the Fpr1 and Fpr2. Fpr1encodes murine FPR1, which is considered the murine orthologue of human FPR. Resveratrol, a non-flavonoid polyphenol rich in red wine and grapes, apart from its beneficial health effects and anti-inflammatory properties, has been reported to reduce neuroinflammation in different neurodegenerative disease models. Resveratrol anti-inflammatory responses involve the activation of the protein deacetylase sirtuin 1 (SIRT1) gene. In this work we have investigated in an LPS-based murine model of neuroinflammation the role of FPR1, examining not only if this receptor undergoes a reduction of its expression during neuroinflammation, but also whether treatment with resveratrol was able to modulate its expression leading to an amelioration of neuroinflammatory picture in a murine model of neuroinflammation. Results of this work showed that FPR1 together with SIRT1 resulted upregulated by resveratrol treatment and that this increase is associated with an amelioration of the neuroinflammatory picture, as demonstrated by the induction of IL-10 and IL1-RA expression and the downregulation of proinflammatory mediators, such as TNF-α and IL-1β. The expression and the modulation of FPR1 by resveratrol may be evaluated in order to propose a novel anti-inflammatory and pro-resolving therapeutic approach for the reduction of the detrimental effects associated with neuro-inflammation based neurodegenerative diseases and also as a promising strategy to promote human health by a diet rich in antioxidative bioactive compounds.

Vitamin C (Vit C) is anutrient present in many foods, particularly citrus fruits, green vegetables, tomatoes, and potatoes. Vit C is studied for its applications in the prevention and management of different pathologies, including neurodegenerative diseases. Neuroinflammation is a defense mechanism activated by a stimulus or an insult that is aimed at the preservation of the brain by promoting tissue repair and removing cellular debris, however, persistent inflammatory responses are detrimental and may lead to the pathogenesis and progression of neurodegenerative diseases like Parkinson’s disease (PD) and Alzheimer’s disease. PD is one of the most common chronic progressive neurodegenerative disorders, and oxidative stress is one of the most important factors involved in its pathogenesis and progression.Due to this, research on antioxidant and anti-inflammatory compounds is an important target for counteracting neurodegenerative diseases, including PD. In the central nervous system, the presence of Vit C in the brain is higher than in other body districts, but why and how this occurs is still unknown. In this research, Vit C, with its anti-inflammatory and anti-oxidative properties, is studied to better understand its contribution to brain protection, in particular, we have investigated the neuroprotective effects of Vit C in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of PD and its role in the modulation of neuroinflammation. First, we observed that Vit C significantly decreased the MPTP-induced loss of tyrosine hydroxylase (TH)-positive dopaminergic neuronal cells in the substantia nigra, as well as microglial cell activation and astrogliosis. Furthermore, gait and spontaneous locomotor activity, evaluated by an automated treadmill and the Open Field test, respectively, were partially ameliorated by Vit C treatment in MPTP-intoxicated animals. In relation to neuroinflammation, results show that Vit C reduced the protein and mRNA expression of inflammatory cytokines such as IL-6, TLR4, TNF-α, iNOS, and CD40, while anti-inflammatory proteins such as IL-10, CD163, TGF-β, and IL-4 increased. Interestingly, we show for the first time that Vit C reduces neuroinflammation by modulating microglial polarization and astrocyte activation. Moreover, Vit C was able to reduce NLRP3 activation, which is linked to the pathogenesis of many inflammatory diseases, including neuroinflammatory disorders. In conclusion, our study provides evidence that Vit C may represent a new promising dietary supplement for the prevention and alleviation of the inflammatory cascade of PD, thus contributing to neuroprotection.

International audience; Several studies have identified a specific metabolic program that is associated with the process of epithelial-mesenchymal transition (EMT). Whereas much is known about the association between glucose metabolism and EMT, the contribution of lipid metabolism is not still completely understood. Here, we studied epithelial and mesenchymal breast cancer cells by proteomic and lipidomic approaches and identified significant differences that characterised these models concerning specific metabolic enzymes and metabolites including fatty acids and phospholipids. Higher levels of monounsaturated fatty acids together with increased expression of enzymes of de novo fatty acid synthesis is the distinct signature of epithelial with respect to mesenchymal cells that, on the contrary, show reduced lipogenesis, higher polyunsaturated fatty acids level and increased expression of genes involved in the triacylglycerol (TAG) synthesis and lipid droplets formation. In the mesenchymal model, the diacylglycerol acyltransferase (DGAT)-1 appears to be the major enzyme involved in TAG synthesis and inhibition of DGAT1, but not DGAT2, drastically reduces the incorporation of labeled palmitate into TAG. Moreover, knockdown of β-catenin demonstrated that this metabolic phenotype in under the control of a network of transcriptional factors and that β-catenin has a specific role in the regulation of lipid metabolism in mesenchymal cells.

In this study, the effects of Radio Electric Asymmetric Conveyer (REAC), a non-invasive physical treatment, on neuroinflammatory responses in a mouse model of parkinsonism induced by intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), were investigated in vivo. We found that the REAC tissue optimization treatment specific for neuro-regenerative purposes (REAC TO-RGN-N) attenuated the inflammatory picture evoked by MPTP-induced nigro-striatal damage in mice, decreasing the levels of pro-inflammatory molecules and increasing anti-inflammatory mediators. Besides, there was a significant reduction of both astrocyte and microglial activation in MPTP-treated mice exposed to REAC TO-RGN-N. These results indicated that REAC TO-RGN-N treatment modulates the pro-inflammatory responses and reduces neuronal damage in MPTP-induced parkinsonism.

This paper presents a step toward the development of a data-centric approach to prevention of Mild Cognitive Impairment and frailty in the elderly population. The scientific literature provides a large number of “indicators” for assessing the quality of behavior for aged individuals, in order to predict possible decaying. On the opposite side, a large variety of sensors and datasets today allows the effective collection of elementary data about actions performed by individuals. This paper proposes to build a bridge between these two sides. In a bottom-up vision, data from sensors and smart cities' datasets are aggregated and interpreted in a way that leads to reliable assessment of the indicators. In a top-down vision, indicators are translated into data analysis. The work described in this paper is part of City4age, a project partially funded by the EU within the H2020 Programme.

Activated microglia secrete an array of pro-inflammatory factors, such as prostaglandins, whose accumulation contributes to neuronal damages. Prostaglandin endoperoxide synthases or cyclooxygenases (COX-1 and COX-2), which play a critical role in the inflammation, are the pharmacological targets of non-steroidal anti-inflammatory drugs, used to treat pain and inflammation. Since it was reported that COX-1 is the major player in mediating the brain inflammatory response, the aim of this study was to evaluate the effects of highly selective COX-1 inhibitors, such as P6 and mofezolac, in neuroinflammation models. Lipopolysaccharide (LPS)-activated mouse BV-2 microglial cells and LPS intracerebroventricular-injected mice as in vitro and in vivo neuroinflammation models, respectively, were used to probe the antiinflammatory efficacy of P6 and mofezolac. Both P6 and mofezolac reduce COX-1 expression in LPS-activated BV-2 cells. This reduction was accompanied with PGE2 release reduction and NF-kB activation downregulation. Coextensively, in the in vivo model, both glial fibrillary acidic protein and ionized calcium-binding adapter molecule-1 expression, two markers of inflammation, were reduced by mofezolac to a rank depending on the encephalon area analyzed. The increase of COX-1 expression observed in all the brain sections of LPS-treated mice was selectively downregulated by the in vivo treatment with mofezolac as well as PGE2 release and Ikβα phosphorylation amount assayed in the brain areas tested. These results indicate the capability of P6 and mofezolac to modulate the NF-kB signaling pathway, emphasizing the neuroprotective effect and therapeutic potential of COX-1 inhibitors in the control of neuroinflammatory diseases.

The most common methods used by neurologist to evaluate Parkinson’s Disease (PD) patients are rating scales, that are affected by subjective and non-repeatable observations. Since several research studies have revealed that walking is a sensitive indicator

Microglia-mediated neuroinflammation has been described as a common hallmark of Parkinson's disease (PD) and is believed to further exacerbate the progressive degeneration of dopaminergic neurons. Current therapies are unable to prevent the disease progression. A significant association has been demonstrated between PD and low levels of vitamin D in patients serum, and vitamin D supplement appears to have a beneficial clinical effect. Herein, we investigated whether vitamin D administered orally in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced preclinical animal model of PD protects against glia-mediated inflammation and nigrostriatal neurodegeneration. Vitamin D significantly attenuated the MPTP-induced loss of tyrosine hydrlase (TH)-positive neuronal cells, microglial cell activation (Iba1-immunoreactive), inducible nitric oxide synthase (iNOS) and TLR-4 expression, typical hallmarks of the pro-inflammatory (M1) activation of microglia. Additionally, Vitamin D was able to decrease pro-inflammatory cytokines mRNA expression in distinct brain areas of the MPTP mouse. Importantly, we also assessed the anti-inflammatory property of vitamin D in the MPTP mouse, in which it upregulated the anti-inflammatory cytokines (IL-10, IL-4 and TGF-β) mRNA expression as well as increasing the expression of CD163, CD206 and CD204, typical hallmarks of alternative activation of microglia for anti-inflammatory signalling (M2). Collectively, these results demonstrate that vitamin D exhibits substantial neuroprotective effects in this PD animal model, by attenuating pro-inflammatory and up-regulating anti-inflammatory processes.