Effects of Human Alpha-Synuclein A53T-A30P Mutations on SVZ and Local Olfactory Bulb Cell Proliferation in a Transgenic Rat Model of Parkinson Disease

A transgenic Sprague Dawley rat bearing the A30P and A53T α-synuclein (α-syn) human mutations under the control of the tyrosine hydroxylase promoter was generated in order to get a better understanding of the role of the human α-syn mutations on the neuropathological events involved in the progression of the Parkinson's disease (PD). This rat displayed olfactory deficits in the absence of motor impairments as observed in most early PD cases. In order to investigate the role of the mutated α-syn on cell proliferation, we focused on the subventricular zone (SVZ) and the olfactory bulbs (OB) as a change of the proliferation could affect OB function. The effect on OB dopaminergic innervation was investigated. The human α-syn co-localized in TH-positive OB neurons. No human α-syn was visualized in the SVZ. A significant increase in resident cell proliferation in the glomerular but not in the granular layers of the OB and in the SVZ was observed. TH innervation was significantly increased within the glomerular layer without an increase in the size of the glomeruli. Our rat could be a good model to investigate the role of human mutated α-syn on the development of olfactory deficits

Human Multipotent Stromal Cells (MSCs) Increase Neurogenesis and Decrease Atrophy of the Striatum in a Transgenic Mouse Model for Huntington's Disease

Background: Implantation of human multipotent stromal cells from bone marrow (hMSCs) into the dentate gyrus of the hippocampus of mice was previously shown to stimulate proliferation, migration and neural differentiation of endogenous neural stem cells. We hypothesized that hMSCs would be beneficial in a mouse model of Huntington disease (HD) due to these neurogenic effects. Results: We implanted hMSCs into the striatum of transgenic mice (N171-82Q) that are a model for HD. The implanted hMSCs rapidly disappeared over 3 to 15 days. However, they increased proliferation and neural differentiation of endogenous neural stem cells for up to 30 days. They also increased neurotrophic signaling and decreased atrophy of the striatum in 3-month old HD mice implanted with hMSCs one month earlier. Conclusions: The results therefore suggested that neural implantation of hMSCs may be of benefit in HD but a number of parameters of dose, treatment schedule, and route of administration need to be optimized

Distinct Roles of Bcl-2 and Bcl-Xl in the Apoptosis of Human Bone Marrow Mesenchymal Stem Cells during Differentiation

Background: Adult mesenchymal stem cells (MSCs) can be maintained over extended periods of time before activation and differentiation. Little is known about the programs that sustain the survival of these cells. Principal Findings: Undifferentiated adult human MSCs (hMSCs) did not undergo apoptosis in response to different cell death inducers. Conversely, the same inducers can readily induce apoptosis when hMSCs are engaged in the early stages of differentiation. The survival of undifferentiated cells is linked to the expression of Bcl-Xl and Bcl-2 in completely opposite ways. Bcl-Xl is expressed at similar levels in undifferentiated and differentiated hMSCs while Bcl-2 is expressed only in differentiated cells. In undifferentiated hMSCs, the down-regulation of Bcl-Xl is associated with an increased sensitivity to apoptosis while the ectopic expression of Bcl-2 induced apoptosis. This apoptosis is linked to the presence of cytoplasmic Nur 77 in undifferentiated hMSCs. Significance: In hMSCs, the expression of Bcl-2 depends on cellular differentiation and can be either pro- or anti-apoptotic. Bcl-Xl, on the other hand, exhibits an anti-apoptotic activity under all conditions

Globular Adiponectin Activates Motility and Regenerative Traits of Muscle Satellite Cells

Regeneration of adult injured skeletal muscle is due to activation of satellite cells, a population of stem cells resident beneath the basal lamina. Thus, information on soluble factors affecting satellite cell activation, as well as migration towards injury and fusion into new myofibers are essential. Here, we show that globular adiponectin (gAd), positively affects several features of muscle satellite cells. gAd activates satellite cells to exit quiescence and increases their recruitment towards myotubes. gAd elicits in satellite cells a specific motility program, involving activation of the small GTPase Rac1, as well as expression of Snail and Twist transcription factors driving a proteolytic motility, useful to reach the site of injury. We show that satellite cells produce autocrine full length adiponectin (fAd), which is converted to gAd by activated macrophages. In turns, gAd concurs to attract to the site of injury both satellite cells and macrophages and induces myogenesis in muscle satellite cells. Thus, these findings add a further role for gAd in skeletal muscle, including the hormone among factors participating in muscle regeneration

Enhancing sexual health and empowerment among migrant women sex workers: a community health worker-led intervention in Marseille, France

IntroductionGiven the high infection rate of sexually transmitted infections (STI) among migrant women sex workers (WSWs), it is necessary to understand how to improve prevention, information and care for this vulnerable population. Community health workers (CHWs), by linking community to health services, are positioned to improve health outcomes in migrant communities. This article aims to describe a pilot innovative intervention performed by CHWs to improve sexual health in migrant WSWs.MethodsThis one-year intervention study used a respondent-driven sampling (RDS) to recruit a representative cohort of migrant WSWs in Marseille, France. Four CHWs were recruited from different communities and participated in all stages of the research. They performed individual and group interventions of prevention, support in care and empowerment. Data on participant characteristics, type of intervention and adherence to the intervention were reported via questionnaires given to participants. Simultaneously, semi-structured interviews and informal interviews of migrant WSW, CHWs and care providers were carried out.ResultsA total of 132 migrant WSWs were included in the cohort. Very few of them knew about PrEP (12%) or already used HIV post-exposure treatment (9%). Migrant WSWs were often victims of rape or racism, 15 and 21%, respectively. In two-thirds of cases the level of health literacy was low. Participants suffered from a combination of vulnerability factors: difficulties with access to social rights, food or housing. Only 13% reported having benefited from medical follow-up or assistance by an NGO in the 3 months prior to the program. By 3 months, more than one third of the participants had been tested for HIV (35%) and 63% knew about PrEP. A total retention rate of 70% was reported in the cohort after 6 months.ConclusionCHWs enabled to improve care access for migrant WSWs by improving the collaboration between care and social actors at a local level. Through these “bring-back-to” interventions for this hard-to-reach population, CHWs enabled an optimization of the care pathway. Our results also highlight the importance of a population-based approach for individual and group support of empowerment interventions in order to strengthen their capacity for action

Human Mesenchymal Stem Cells Prolong Survival and Ameliorate Motor Deficit through Trophic Support in Huntington's Disease Mouse Models

We investigated the therapeutic potential of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in Huntington's disease (HD) mouse models. Ten weeks after intrastriatal injection of quinolinic acid (QA), mice that received hBM-MSC transplantation showed a significant reduction in motor function impairment and increased survival rate. Transplanted hBM-MSCs were capable of survival, and inducing neural proliferation and differentiation in the QA-lesioned striatum. In addition, the transplanted hBM-MSCs induced microglia, neuroblasts and bone marrow-derived cells to migrate into the QA-lesioned region. Similar results were obtained in R6/2-J2, a genetically-modified animal model of HD, except for the improvement of motor function. After hBM-MSC transplantation, the transplanted hBM-MSCs may integrate with the host cells and increase the levels of laminin, Von Willebrand Factor (VWF), stromal cell-derived factor-1 (SDF-1), and the SDF-1 receptor Cxcr4. The p-Erk1/2 expression was increased while Bax and caspase-3 levels were decreased after hBM-MSC transplantation suggesting that the reduced level of apoptosis after hBM-MSC transplantation was of benefit to the QA-lesioned mice. Our data suggest that hBM-MSCs have neural differentiation improvement potential, neurotrophic support capability and an anti-apoptotic effect, and may be a feasible candidate for HD therapy

Dynamique des trous noirs en milieu gazeux

Black holes are ubiquitous in the Universe and supermassive black holes are observed at the centre of most galaxies. The correlations observed between these supermassive black holes and their host galaxies suggest a common history. Black holes are now seen as key components in the evolution of galaxies, helping to regulate gas and stars. A black hole accretes matter and releases gravitational energy that acts in return on its environment, providing feedback. The angular momentum or spin of black holes has a direct influence on the fraction of energy released and radiated during accretion phases.The growth of black holes is based on a secular evolution interspersed with galaxy mergers. Their spin evolves during gas accretion phases and during black hole coalescences. Moreover, galaxy mergers can play an important role in promoting gas accretion peaks and the eventual coalescence of black holes. In this context, I have performed idealized simulations of galaxy mergers including the evolution of supermassive black holes mass and spin in order to determine possible evolutionary trends depending on the orbital configuration of the encounter.The coalescence of black holes depends on their ability to lose angular momentum to reach the centre of the merging galaxy. On the scale of the kpc that initially separate the black holes, the main driver of their orbital decay is dynamical friction. The role of dynamical friction exerted in particular by the gas is still poorly understood. Simulations of galaxy mergers do not resolve the scale of this phenomenon and its inclusion relies on models developed for a homogeneous gaseous medium. I have studied dynamical friction in a turbulent gaseous medium using high-resolution hydrodynamic simulations with turbulent forcing.Les trous noirs sont omniprésents dans l'Univers et on observe des trous noirs supermassifs au cœur de la plupart des galaxies. Les corrélations observées entre ces trous noirs supermassifs et leur galaxies hôtes laissent penser à une histoire commune. Les trous noirs sont aujourd'hui envisagés comme des pièces maîtresses de l'évolution des galaxies, participant à la régulation du gaz et des étoiles. Un trou noir accrète de la matière et libère une part d'énergie gravitationnelle qui agit en retour sur son environnement, fournissant une rétroaction. Le moment angulaire ou spin des trous noirs a une influence directe sur la fraction d'énergie libérée et rayonnée pendant les périodes d'accrétion. La croissance des trous noirs repose sur une évolution séculaire entrecoupée d'épisodes de fusion de galaxies. Leur spin évolue lors des phases d'accrétion de gaz et lors des coalescences de trous noirs. Par ailleurs les fusions de galaxies peuvent jouer un rôle important en favorisant des pics d'accrétion de gaz et l'éventuelle coalescence des trous noirs. Dans ce contexte, j'ai réalisé des simulations idéalisées de fusion de galaxies incluant l'évolution de la masse et du spin des trous noirs supermassifs afin de déterminer d'éventuelles tendances d'évolution en fonction de la configuration orbitale de la rencontre. La coalescence des trous noirs dépend leur capacité à perdre du moment angulaire pour rejoindre le centre de la galaxie résultante d'une fusion. A l'échelle des kpc qui séparent initialement les trous noirs, le principal moteur de leur décroissance orbitale est la friction dynamique. Le rôle de la friction dynamique exercée en particulier par le gaz est encore mal connu. Les simulations de fusion de galaxies ne résolvent pas l'échelle de ce phénomène et sa prise en compte repose sur des modèles développés pour un milieu gazeux homogène. J'ai étudié la friction dynamique dans un milieu gazeux turbulent à l'aide de simulations hydrodynamiques haute résolution avec un forçage turbulent