Counteracting neuroinflammation in experimental Parkinson's disease favors recovery of function : effects of Er-NPCs administration

Background Parkinson\u2019s disease (PD) is the second most common neurodegenerative disease, presenting with midbrain dopaminergic neurons degeneration. A number of studies suggest that microglial activation may have a role in PD. It has emerged that inflammation-derived oxidative stress and cytokine-dependent toxicity may contribute to nigrostriatal pathway degeneration and exacerbate the progression of the disease in patients with idiopathic PD. Cell therapies have long been considered a feasible regenerative approach to compensate for the loss of specific cell populations such as the one that occurs in PD. We recently demonstrated that erythropoietin-releasing neural precursors cells (Er-NPCs) administered to MPTP-intoxicated animals survive after transplantation in the recipient\u2019s damaged brain, differentiate, and rescue degenerating striatal dopaminergic neurons. Here, we aimed to investigate the potential anti-inflammatory actions of Er-NPCs infused in an MPTP experimental model of PD. Methods The degeneration of dopaminergic neurons was caused by MPTP administration in C57BL/6 male mice. 2.5\u2009 7\u2009105 GFP-labeled Er-NPCs were administered by stereotaxic injection unilaterally in the left striatum. Functional recovery was assessed by two independent behavioral tests. Neuroinflammation was investigated measuring the mRNAs levels of pro-inflammatory and anti-inflammatory cytokines, and immunohistochemistry studies were performed to evaluate markers of inflammation and the potential rescue of tyrosine hydroxylase (TH) projections in the striatum of recipient mice. Results Er-NPC administration promoted a rapid anti-inflammatory effect that was already evident 24\u2009h after transplant with a decrease of pro-inflammatory and increase of anti-inflammatory cytokines mRNA expression levels. This effect was maintained until the end of the observational period, 2\u2009weeks post-transplant. Here, we show that Er-NPCs transplant reduces macrophage infiltration, directly counteracting the M1-like pro-inflammatory response of murine-activated microglia, which corresponds to the decrease of CD68 and CD86 markers, and induces M2-like pro-regeneration traits, as indicated by the increase of CD206 and IL-10 expression. Moreover, we also show that this activity is mediated by Er-NPCs-derived erythropoietin (EPO) since the co-injection of cells with anti-EPO antibodies neutralizes the anti-inflammatory effect of the Er-NPCs treatment. Conclusion This study shows the anti-inflammatory actions exerted by Er-NPCs, and we suggest that these cells may represent good candidates for cellular therapy to counteract neuroinflammation in neurodegenerative disorders

Le esperienze sfavorevoli infantili, le conseguenze, il pediatra

Il maltrattamento e l\u2019abuso non sono fenomeni attuali ma una realt\ue0 antica, spesso ignorata a volte tollerata e giustificata. Nel 1963, Kempe pediatra USA, precursore del movimento della tutela dei minori, riteneva che il riconoscimento, lo studio del fenomeno, la ricerca di strumenti e di risorse efficaci potessero contrastare la violenza ai danni dei minori

Matthew’s 25 Ministries City of Refuge: analisi di una forma alternativa di reinserimento sociale dei “sex offender”

Il tema del trattamento dei sex offender \ue8 di respiro internazionale. Si pensi, ad esempio, agli Stati Uniti d\u2019America dove la legislazione che disciplina questa tipologia di reati \ue8 estremamente restrittiva nei confronti di coloro che hanno gi\ue0 scontato la propria condanna, soprattutto per quanto concerne i luoghi di residenza, di transito e di lavoro. L\u2019obiettivo dell\u2019intervento \ue8 volto a presentare ed analizzare un recente progetto, sviluppato in Florida, stato noto per la durezza delle pene e delle limitazioni imposte dopo il periodo detentivo nei confronti dei cosiddetti \u201csex offender\u201d, al fine di favorirne la reintegrazione nella societ\ue0. Fondata nel 2009 dal reverendo Richard Whiterow, Matthew\u2019s 25 Ministries City of Refuge, pi\uf9 nota come Miracle Village, \ue8 una cittadina di 200 abitanti la cui maggioranza \ue8 rappresentata da ex \u2013 sex offender. Caratteristica principale di questo luogo \ue8 la fondamentale lontananza di cinque km dal pi\uf9 vicino centro abitato , fattore che permette ai sex offender, altrimenti spesso emarginati, di condurre una vita normale e di diminuire, cos\uec, il rischio di recidiva o di commissione di altri reati, per lo pi\uf9 di genere appropriativo. Non tutti i sex-offender possono accedere alla comunit\ue0: un dettagliato controllo sulla tipologia di reato sessuale commesso viene effettuato ad ogni richiesta e l\u2019ingresso \ue8 negato agli autori di reati sessuali pi\uf9 gravi. Questo intervento vuole analizzare Matthew\u2019s 25 Ministries City of Refuge in chiave criminologica, associando un approccio di tipo quantitativo, con un\u2019analisi dei dati relativi alle possibilit\ue0 di recidiva e all\u2019impatto di una rigida legislazione sulla comunit\ue0, ad uno qualitativo, caratterizzato da un\u2019intervista ottenuta dall\u2019attuale operations director della cittadina, Ted Rodarm, cos\uec da declinare in modo esaustivo la natura di questa comunit\ue0 e i possibili benefici derivanti da essa

Intimate Partner Violence: A Glimpse From Italy’s Largest Domestic Violence Center

BACKGROUND AND AIMS Domestic violence is defined by the U.N. as the kind of violence perpetrated by intimate partners such as physical, psychological and economic abuse (U.N. 1993). The center for domestic and sexual abused victims has been founded in 1996. At the beginning the main task was to help the sexual abused victims in the province of Milan; a decade later the domestic violence offences have been included in the activities of the center. The present study is going to describe the data retrieved during its lifetime, showing the change in the trends and focusing on the analysis of the years included between 2012 and 2014. MATERIALS AND METHODS The staff of the center has retrieved raw data since its foundation, which have been analyzed in order to define the features of these events. A report is filled out for each victim including all the variables relevant to the comprehension of the phenomenon, such as the sociological, psychological and medico legal aspects of the crime. RESULTS The preliminary evaluation of the data shows a clear trend towards a constant rise in the requests for supporting help for both types of violence with an increase of 409% from 1996 to 2015 related to sexual violence and a 124% increase in domestic violence between 2008 and 2015; it has also been observed a growth in the spontaneous recover by the victims. Throughout the evaluation it appears that the number of males reporting domestic abuse might be constantly increasing from 1 case to 13 between 2012 and 2014. This may also be due to an increased conscience by the abused males. Other interesting trends have been detected related to child witnessing domestic violence, showing an increasing trend from 5,5% to 16% that might be also related to the increase of abuses perpetrated by both parents which varied from 4% to 16%; moreover, it appears that the most victimized age group is 31 \u2013 40 firmly standing between 33% and 37%. We were not able to detect significant difference between domestic violence and sexual violence, in fact the overlap between those two kinds of violence is very weak, it ranges from 0,6% to 1,6%. CONCLUSIONS In summary, the information retrieved during this initial analysis leads to an improved understanding of the phenomenon, and reinforces our idea that the final purpose of the study on the development of prevention policies may be achieved. We shall further analyze the relationship between different variables such as the most victimized nationalities and the revictimization trend. REFERENCES U.N. (1993), \u201cGeneral Assembly: Declaration on the Elimination of Violence Against Women\u201

Prevenzione e Cura del Trauma Psicologico: le Esperienze Sfavorevoli Infantili (ESI) prevenzione e cura dei traumi subiti

Il trauma psicologico \ue8 un\u2019esperienza complessa che influisce sullo sviluppo del bambino e dell\u2019adolescente. I partecipanti saranno coinvolti in attivit\ue0 pratiche dove sperimenteranno in modo concreto le modalit\ue0 per l\u2019identificazione e la presa in carico delle esperienze traumatiche sia a livello individuale sia attraverso efficaci modelli organizzativi

Distinguishing incised wounds in asylum seekers as ritual scarification or torture: a cross road between physical and cultural anthropology

Beating is the most common method to torture. But it appears that the use of sharp-edged weapon is the main method that leaves scars. Such weapons are used in four different ways; self-harming, torture and other cruel, inhuman and degrading treatments (CIDT) and ritual scarifications. In order to analyze the previously mentioned topic, we proposed two insights of the issue: one related to the medico \u2013 legal field and the other one pertaining to cultural anthropology. This study aims to determine if lesions due to ritual scarifications can be distinguished from the other type of incised wounds. The medical report of 115 political refugees and asylum seekers from the Medico-Legal Institute of Milan (Italy) have been studied. A dataset on Excel (Microsoft) has been created to understand the circumstances the number, and the localization of their scars due to sharp-edged weapons. From the 115 victims, 45.2% showed incised wounds; 14.7% showed signs of torture; 23.4% presented CIDT evidences. Finally, two other categories were represented in the sample: ritual scarification, counting 6 cases and two individuals who reported self \u2013 harming. The African continent is over-represented. It appears that the scarification process shows a pattern. The lesions for some cases can be distinguished from self-harm, torture and CIDT. Scarifications are made for social, medical, religious or magical purposes. Problems are raised when cases of alleged torture show physical lesions that fit with patterns of ritual scarifications. Cultural and social backgrounds play then an important role during medico-legal visits. Ritual scarifications are still relatively practiced among African countries. Only a trend for such lesions can be identified. Knowing all type of scarifications and being able to read them can be a huge step for the medico-legal identification

Purification from black widow spider venom of a protein factor causing the depletion of synaptic vesicles at neuromuscular junctions

The aqueous extract of the venom glands of black widow spiders was fractionated on a column of Sephadex G-200 and then on a column of DEAE-Sephadex A-50 pH 8.2. A protein fraction was obtained that caused a great increase in the frequency of occurrence of miniature end plate potentials at the frog neuromuscular junction, and caused swelling of the nerve terminals and depleted them of their vesicles. The fraction consists of a least four protein components that are similar in their molecular weights (about 130,000) and isoelectric points (ranging from pH 5.2 to 5.5) and are immunologically indistinguishable. It contains no sugar residues and has little or no lipolytic or proteolytic activity. The fraction is toxic to mice and is different from the fractions that act on houseflies, the crayfish stretch receptor and the cockroach heart. It seems pure enough to warrant a detailed study of its site and mode of action

HuR’s interaction with lincBRN1a and lincBRN1b is implicated in neuronal stem cells differentiation

INTRODUCTION: LncRNAs play crucial roles in cellular processes but their regulatory effects in the adult brain and neural stem cells (NSCs) remain to be entirely characterized. Interestingly, it has been shown that genetic ablation of specific lncRNAs can cause strong modifications in mouse brain\u2019s development. RESULTS: Here, we demonstrate that 10 lncRNAs (LincENC1, FABL, lincp21, HAUNT, PERIL, lincBRN1a, lincBRN1b, HOTTIP, TUG1 and FENDRR) are deregulated during murine NSCs differentiation. By RNA immunoprecipitation assay we show that they interact with the RNA binding protein ELAVL1/HuR. Furthermore, we characterize the function of two of the deregulated lncRNAs, lincBRN1a and lincBRN1b, during NSCs\u2019 differentiation. Their inhibition leads to the induction of differentiation, with a concomitant decrease in stemness and increase in neuronal markers, indicating that they exert key functions in neuronal cells differentiation. The treatment with actinomycin D, a transcriptional inhibitor, allowed to evaluate the half-life of these RNA molecules, and we found that HuR\u2019s inhibition lead to a modification in their decay rates both in neural stem cells and in differentiated ones. We also identify the human homologs of the mentioned 10 lncRNAs and we report their deregulation during human iPSCs differentiation into neurons. Figure 1: Expression analysis of lncRNAs in NSCs and during differentiation (d1, d3, d8). DISCUSSION & CONCLUSIONS: Our results show that these lncRNAs play a role in neural stem cells biology influencing their differentiation capabilities, as the alteration of their levels may have an effect on this process. Moreover, we report that the inhibition of HuR\u2019s interaction with the analyzed lncRNAs leads to neural differentiation, suggesting a complementary role for the lncRNAs and the RNA-binding protein (HuR) in this process. The study of their expression in human iPSCs differentiation into neurons suggest that our results could also be applied to human neuronal development. ACKNOWLEDGEMENTS: The authors are deeply grateful to Professor Alfredo Gorio (University of Milan, Italy) for his scientific support and unswerving encouragement to the work. Moreover, authors acknowledge the economic support by FAIP (Federazione Associazioni Italiane Paratetraplegici), \u201cNeurogel-en-March\u201d Foundation (France) to AG, Fondazione \u201cRomeo and Enrica Invernizzi\u201d to AMDG, Fondazione Regionale per la Ricerca Biomedica (FRRB) (Regione Lombardia, TRANS_ALS, project nr. 2015-0023, to AG, AMDG and CC). Federica Rey would like to acknowledge and thank the Fondazione Fratelli Confalonieri for financial support during her PhD

HuR’s interaction with lincBRN1a and lincBRN1b is implicated in neuronal stem cells differentiation

Background. LncRNAs play crucial roles in cellular processes but their regulatory effects in the adult brain and neural stem cells (NSCs) remain to be entirely characterized. Interestingly, it has been shown that genetic ablation of specific lncRNAs can cause strong impairments in mouse brain\u2019s development. Results. Here, we demonstrate that 10 lncRNAs (LincENC1, FABL, lincp21, HAUNT, PERIL, lincBRN1a, lincBRN1b, HOTTIP, TUG1 and FENDRR) are deregulated during murine NSCs differentiation. By RNA immunoprecipitation assay we show that they interact with the RNA binding protein ELAVL1/HuR. Furthermore, we characterize the function of two of the deregulated lncRNAs, lincBRN1a and lincBRN1b, during NSCs\u2019 differentiation. Their inhibition obtained by siRNA approach leads to the induction of differentiation, with a concomitant decrease in stemness and increase in neuronal markers, indicating that they exert key functions in neuronal cells differentiation. The treatment with the transcriptional inhibitor actinomycin D allowed the evaluation of the half-lives of these RNA molecules. Moreover, we found that the HuR\u2019s inhibition, by siRNA or by using the specific pharmacological inhibitor dihydrotanshinone I, leads to a modification of lincBRN1a and lincBRN1b\u2019s decay rates both in NSCs and in differentiated ones. We also identified six human homologs of the ten lncRNAs studied in mice and we report their deregulation during human iPSCs differentiation into neurons. Conclusions. Our results show that lincBRN1a and lincBRN1b play a role in NSCs biology influencing their differentiation capabilities, as the alteration of their levels may have an effect on this process. Moreover, we report that the inhibition of HuR\u2019s interaction with the analyzed lncRNAs leads to neural differentiation, suggesting a complementary role for the lncRNAs and HuR in stemness. The study of their expression in human iPSCs differentiation into neurons suggest that our results could also be applied to human neuronal development

Treatment of peripheral neuropathies.

There are three general approaches to treatment of peripheral neuropathy. First, an attempt should be made to reverse the pathophysiological process if its nature can be elucidated. Second, nerve metabolism can be stimulated and regeneration encouraged. Third, even if the neuropathy itself cannot be improved, symptomatic therapy can be employed. This review outlines the options available for each approach