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Oligodendrocyte progenitor cells (OPCs) represent a subtype of glia, giving rise to oligodendrocytes, the myelin-forming cells in the central nervous system (CNS). While OPCs are highly proliferative during development, they become relatively quiescent during adulthood, when their fate is strictly influenced by the extracellular context. In traumatic injuries and chronic neurodegenerative conditions, including those of autoimmune origin, oligodendrocytes undergo apoptosis, and demyelination starts. Adult OPCs become immediately activated; they migrate at the lesion site and proliferate to replenish the damaged area, but their efficiency is hampered by the presence of a glial scar-a barrier mainly formed by reactive astrocytes, microglia and the deposition of inhibitory extracellular matrix components. If, on the one hand, a glial scar limits the lesion spreading, it also blocks tissue regeneration. Therapeutic strategies aimed at reducing astrocyte or microglia activation and shifting them toward a neuroprotective phenotype have been proposed, whereas the role of OPCs has been largely overlooked. In this review, we have considered the glial scar from the perspective of OPCs, analysing their behaviour when lesions originate and exploring the potential therapies aimed at sustaining OPCs to efficiently differentiate and promote remyelination.

(1) Background: This study evaluates, one year later, the levels of burnout, anxious-depressive, and post-traumatic symptoms and the general health status in the Health Workers (HWs) involved in the SARS-COVID-19 pandemic in the Novara area. (2) Methods: The survey was sent via a link in an email to doctors, nurses, and other operators during the period between June and August 2021. The survey collected socio-demographic data and contained some self-administered questionnaires. (3) Results: A total of 688 HWs completed the survey, 53% were aged 30-49 years, 68% were female, 76% were cohabiting, 55% had children, 86% reported family habit changes, and 20% had non-COVID related health problems. Only a few of the respondents had a follow-up by a specialist (12%), of which there were even less in recent times (6%). It was observed that the respondents had undergone burnout; a poor state of general mental health (62%); depressive symptoms (70%); post-traumatic symptoms (29%); and less frequently, anxious symptoms (16%). The data of this study are in line with other studies in the literature. (4) Conclusions: The data indicate that psychological-based suffering was no longer markedly concentrated in some specific bands of HWs. In conclusion, it would be essential to enhance HW support strategies.

Extracellular vesicles (EVs) have been increasingly recognized as essential players in cell communication in many organs and systems, including the central nervous system (CNS). A proper interaction between neural cells is fundamental in the regulation of neurophysiological processes and its alteration could induce several pathological phenomena, such as neurodegeneration, neuroinflammation, and demyelination. EVs contain and transfer complex molecular cargoes typical of their cells of origin, such as proteins, lipids, carbohydrates, and metabolites to recipient cells. EVs are also enriched in non-coding RNAs (e.g., microRNAs, lncRNAs, and circRNA), which were formerly considered as cell-intrinsic regulators of CNS functions and pathologies, thus representing a new layer of regulation in the cell-to-cell communication. In this review, we summarize the most recent and advanced studies on the role of EV-derived ncRNAs in the CNS. First, we report the potential of neural stem cell-derived ncRNAs as new therapeutic tools for neurorepair. Then, we discuss the role of neuronal ncRNAs in regulating glia activation, and how alteration in glial ncRNAs influences neuronal survival and synaptic functions. We conclude that EV-derived ncRNAs can act as intercellular signals in the CNS to either propagate neuroinflammatory waves or promote reparative functions.

In the mature central nervous system (CNS), oligodendrocytes (OLs) provide support and insulation to axons thanks to the production of a myelin sheath. During their maturation to myelinating cells, OLs require energy and building blocks for lipids, which implies a great investment of energy fuels and molecular sources of carbon. The oligodendroglial G protein-coupled receptor 17 (GPR17) has emerged as a key player in OL maturation; it reaches maximal expression in pre-OLs, but then it has to be internalized to allow terminal maturation. In this study, we aim at elucidating the role of physiological GPR17 downregulation in OL metabolism by applying transcriptomics, metabolomics and lipidomics on differentiating OLs. After GPR17 silencing, we found a significant increase in mature OL markers and alteration of several genes involved in glucose metabolism and lipid biosynthesis. We also observed an increased release of lactate, which is partially responsible for the maturation boost induced by GPR17 downregulation. Concomitantly, GPR17 depletion also changed the kinetics of specific myelin lipid classes. Globally, this study unveils a functional link between GPR17 expression, lactate release and myelin composition, and suggests that innovative interventions targeting GPR17 may help to foster endogenous myelination in demyelinating diseases.

The COVID-19 pandemic has tested the performance of hospitals and intensive care units around the world. Health care workers (HCWs) have been used to developmental symptoms, but this was especially true during the COVID-19 pandemic when HCWs have been faced with many other sources of stress and anxiety that can usually be avoided. Moreover, long-term shifts and unprecedented population restrictions have weakened people's ability to cope with stress. The research aims to observe the dynamic interplay between burnout, depression, distress, and anxiety in HCWs working in various settings, with specific a focus on emotional exhaustion, depersonalization, and a diminished sense of personal achievement in mediating a worse mental health status during the first wave of the COVID-19 pandemic in Italy. We performed a mediation analysis, which resulted in a strong correlation among depression, psychological distress, health perception and anxiety, and the impact of job burnout on anxiety, depression, and distress. Gender seemed to have a strong correlation with burnout, anxiety, and distress; the impact of the COVID-19 pandemic on Quality of Life seemed to affect anxiety and depression; the possible changes in job tasks and duties (intended as a change in work area or location and role change)influenced depression and job burnout. Encouraging supportive and educational strategies would be recommended to policymakers.

Wildland fires, increasing in recent decades in the Mediterranean region due to climate change, can contribute to PM levels and composition. This study aimed to investigate biological effects of PM 2.5 (Ø < 2.5 µm) and PM 10 (Ø < 10 µm) collected near a fire occurred in the North-West of Italy in 2017 and in three other areas (urban and rural areas). Organic extracts were assessed for mutagenicity using Ames test (TA98 and TA100 strains), cell viability (WST-1 and LDH assays) and genotoxicity (Comet assay) with human bronchial cells (BEAS-2B) and estrogenic activity using a gene reporter assay (MELN cells). In all sites, high levels of PM 10 and PM 2.5 were measured during the fire suggesting that near and distant sites were influenced by fire pollutants. The PM 10 and PM 2.5 extracts induced a significant mutagenicity in all sites and the mutagenic effect was increased with respect to historical data. All extracts induced a slight increase of the estrogenic activity but a possible antagonistic activity of PM samples collected near fire was observed. No cytotoxicity or DNA damage was detected. Results confirm that fires could be relevant for human health, since they can worsen the air quality increasing PM concentrations, mutagenic and estrogenic effects.

In multiple sclerosis (MS), oligodendrocyte precursor cells (OPCs) are recruited to the site of injury to remyelinate damaged axons; however, in patients this process is often ineffective due to defects in OPC maturation. The membrane receptor GPR17 timely regulates the early stages of OPC differentiation; however, after reaching its highest levels in immature oligodendrocytes, it has to be downregulated to allow terminal maturation. Since, in several animal models of disease GPR17 is upregulated, the aim of this work was to characterize GPR17 alterations in MS patients. We developed immunohistochemistry and immunofluorescence procedures for the detection of GPR17 in human tissues and stained post-mortem MS brain lesions from patients with secondary progressive MS and control subjects. The inflammatory activity in each lesion was evaluated by immunohistochemistry for the myelin protein MOG and the HLA antigen to classify them as active, chronic inactive or chronic active. Hence, we assessed the distribution of GPR17-positive cells in these lesions compared to normal appearing white matter (NAWM) and white matter (WM) of control subjects. Our data have shown a marked increase of GPR17-expressing oligodendroglial cells accumulating at NAWM, in which moderate inflammation was also found. Furthermore, we identified two distinct subpopulations of GPR17-expressing oligodendroglial cells, characterized by either ramified or rounded morphology, that differently populate the WM of healthy controls and MS patients. We concluded that the coordinated presence of GPR17 in OPCs at the lesion sites and inflamed NAWM areas suggests that GPR17 could be exploited to support endogenous remyelination through advanced pharmacological approaches.