Search

Background Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia in the world. Microglia are the innate immune cells of CNS; their proliferation, activation, and survival in pathologic and healthy brain have previously been shown to be highly dependent on CSF1R. Methods Here, we investigate the impact of such receptor on AD etiology and microglia. We deleted CSF1R using Cre/Lox system; the knockout (KO) is restricted to microglia in the APP/PS1 mouse model. We induced the knockout at 3 months old, before plaque formation, and evaluated both 6- and 8-month-old groups of mice. Results Our findings demonstrated that CSF1R KO did not impair microglial survival and proliferation at 6 and 8 months of age in APP cKO compared to their littermate-control groups APPSwe/PS1. We have also shown that cognitive decline is delayed in CSF1R-deleted mice. Ameliorations of AD etiology are associated with a decrease in plaque volume in the cortex and hippocampus area. A compensating system seems to take place following the knockout, since TREM2/β-Catenin and IL-34 expression are significantly increased. Such a compensatory mechanism may promote microglial survival and phagocytosis of Aβ in the brain. Conclusions Our results provide new insights on the role of CSF1R in microglia and how it interacts with the TREM2/β-Catenin and IL-34 system to clear Aβ and ameliorates the physiopathology of AD.

Multiple sclerosis and Alzheimer’s disease are two complex neurodegenerative diseases involving the immune system. So far, available treatments provide at best mild improvements to patients’ conditions. For decades now, a new set of molecules have been used to modulate and regulate the innate immunity in these pathologies. Most studies have been carried out in rodents and some of them have reported tremendous beneficial effects on the disease course. The modulation of innate immune cells is of great interest since it provides new hope for patients. In this review, we will briefly overview the therapeutic potential of some molecules and receptors in multiple sclerosis and Alzheimer’s disease and how they could be used to exploit new therapeutic avenues.

SummaryWomen die less than men of COVID-19, but have been more concerned about its health consequences and more compliant with the public health rules imposed during the pandemic. Since return to normal life depends on vaccination, but delays in acceptance or outright refusals of vaccination are already evident, we investigate gender differences in attitudes and expected behaviors regarding COVID-19 vaccination. Using original data from a survey conducted in December 2020 in ten developed countries (N=13,326), we discover aCOVID-19 Vaccine’s gender paradox. Being more concerned about COVID-19 and more likely to believe to be infected and consequently to become seriously ill, women could be expected to be more supportive of vaccination than men. Instead, our findings show that women agree less than men to be vaccinated and to make vaccination compulsory. Our evidence suggests that their vaccine hesitance is partly due skepticism, since women are less likely to believe that vaccination is the only solution to COVID-19 and more likely to believe that COVID-19 was created by large corporations. Using a survey experiment performed in these ten countries, we show that information provision on the role of vaccination to become immune to COVID-19 is effective in reducing vaccine hesitance.

The initial public health response to the breakout of COVID-19 required fundamental changes in individual behavior, such as isolation at home or wearing masks. The effectiveness of these policies hinges on generalized public obedience. Yet, people’s level of compliance may depend on their beliefs regarding the pandemic. We use original data from two waves of a survey conducted in March and April 2020 in eight Organisation for Economic Co-operation and Development countries (n = 21,649) to study gender differences in COVID-19−related beliefs and behaviors. We show that women are more likely to perceive COVID-19 as a very serious health problem, to agree with restraining public policy measures, and to comply with them. Gender differences in attitudes and behavior are sizable in all countries. They are accounted for neither by sociodemographic and employment characteristics nor by psychological and behavioral factors. They are only partially mitigated for individuals who cohabit or have direct exposure to the virus. We show that our results are not due to differential social desirability bias. This evidence has important implications for public health policies and communication on COVID-19, which may need to be gender based, and it unveils a domain of gender differences: behavioral changes in response to a new risk.

Microglia are the brain resident immune cells; they can produce a large variety of growth factors (GFs) to prevent neuronal damages and promote recovery. In neurodegenerative diseases, microglia can play both benefic and deleterious roles, depending on different factors and disease context. In multiple sclerosis, microglia are involved in both demyelination (DM) and remyelination (RM) processes. Recent studies suggest a beneficial role of microglia in regenerative processes. These include the regenerative development of myelin after DM. This review gives an overlook of how microglia and GFs can influence the RM properties.

Microglia are the innate immune cells of the CNS and their proliferation, activation, and survival have previously been shown to be highly dependent on macrophage colony-stimulating factor receptor (CSF1R). Here we investigated the impact of the receptor in such processes using two different models of nerve injuries, namely hypoglossal axotomy and cuprizone-induced demyelination. Both models are associated with a robust microgliosis. The role of CSF1R was investigated using the gene deletion Cre/Lox system, which allows the conditional knock-out following tamoxifen administration. We found that after 5 weeks of cuprizone diet that CSF1R suppression caused a significant impairment of microglia function. A reduced microgliosis was detected in the corpus collosum of CSF1R knock-out mice compared to controls. In contrast to cuprizone model, the overall number of Iba1 cells was unchanged at all the times evaluated following hypoglossal axotomy in WT and cKO conditions. After nerve lesion, a tremendous proliferation was noticed in the ipsilateral hypoglossal nucleus to a similar level in both knock-out and wild-type groups. We also observed infiltration of bone-marrow derived cells specifically in CSF1R-deficient mice, these cells tend to compensate the CSF1R signaling pathway suppression in resident microglia. Taking together our results suggest a different role of CSF1R in microglia depending on the model. In the pathologic context of cuprizone-induced demyelination CSF1R signaling pathway is essential to trigger proliferation and survival of microglia, while this is not the case in a model of systemic nerve injury. M-CSF/CSF1R is consequently not the unique system involved in microgliosis following nerve damages.

Macrophage colony-stimulating factor (mCSF) is a cytokine known to promote the recruitment of macrophages inducing the release of CCL2, a chemokine mobilizing monocytes to sites of inflammation. Additionally, it induces microglia/macrophage proliferation and the polarization of these cells towards a M2-like phenotype, impairing their ability to release pro-inflammatory factors and toxic mediators, while favoring the release of mediators promoting tissue repair. Another important player is the mCSF receptor CSFR1, which is highly expressed in monocytes, macrophages and microglia. Here, we discuss the new interesting therapeutic avenue of the mCSF/CSFR1 axis on brain diseases. More specifically, mCSF cascade might stimulate the survival/proliferation of oligodendrocytes, enhance the immune response as well as modulate the release of growth factors and the phagocytic activity of immune cells to remove myelin debris and toxic proteins from the brain.

Background Multiple sclerosis is a neurodegenerative disorder characterized by myelin loss in the brain parenchyma. To mimic the disease, mice are fed a cuprizone-supplemented diet for 5 weeks, which leads to demyelination of white and grey matter regions, with the corpus callosum being the most susceptible to cuprizone intoxication. Although this model is highly exploited, classical behavioural tests showed inconsistent results. Objective In our study, we aimed to use the automated system Intellicage to phenotype the behaviour of cuprizone-fed mice. Methods Mice were continuously monitored during the 5 weeks of intoxication in their home cages, with minimal interference from the experimenter. Mice were assessed for spontaneous activity, fine movements, and impulsivity. Results Consistently, cuprizone-fed mice showed reduced activity and impulsivity throughout the test period. These behavioral results were confirmed by repeating the battery of behavioral tests in a second cohort of cuprizone-fed mice. Our results suggest that the behavioural phenotyping of cuprizone-fed mice using Intellicage is reproducible and sensitive enough to detect changes normally missed in standard behavioral test batteries. Conclusion Using a reproducible and standardized method to assess behavioral changes in mice intoxicated with cuprizone is crucial to better understand the disease as well as the functional outcome of treatments.

The purinergic receptor P2Y6 is expressed in immune cells, including the microglia that are implicated in neurological disorders. Its ligand, UDP, is a signaling molecule that can serve as an “find-me” signal when released in significant quantities by damaged/dying cells. The binding of UDP by P2Y6R leads to the activation of different biochemical pathways, depending on the disease context and the pathological environment. Generally, P2Y6R stimulates phagocytosis. However, whether or not phagocytosis coincides with cell activation or the secretion of pro-inflammatory cytokines needs further investigation. The current review aims to discuss the various functions of P2Y6R in some CNS disorders. We present evidence that P2Y6R may have a detrimental or beneficial role in the nervous system, in the context of neurological pathologies, such as ischemic stroke, Alzheimer’s disease, Parkinson’s disease, radiation-induced brain injury, and neuropathic pain.

Background Improving patients’ tuberculosis (TB) knowledge is a salient component of TB control strategies. Patient knowledge of TB may encourage infection prevention behaviors and improve treatment adherence. The purpose of this study is to examine how TB knowledge and infection prevention behaviors change over the course of treatment. Methods A matched patient-health worker dataset (n = 6,031) of publicly treated TB patients with NGO-provided treatment support health workers was compiled in nine Indian cities from March 2013 to September 2014. At the beginning and end of TB treatment, patients were asked about their knowledge of TB symptoms, transmission, and treatment and infection prevention behaviors. Results Patients beginning TB treatment (n = 3,424) demonstrated moderate knowledge of TB; 52.5% (50.8%, 54.2%) knew that cough was a symptom of TB and 67.2% (65.6%, 68.7%) knew that TB was communicable. Overall patient knowledge was significantly associated with literacy, education, and income, and was higher at the end of treatment than at the beginning (3.7%, CI: 3.02%, 4.47%). Infection prevention behaviors like covering a cough (63.4%, CI: 61.2%, 65.0%) and sleeping separately (19.3%, CI: 18.0%, 20.7%) were less prevalent. The age difference between patient and health worker as well as a shared language significantly predicted patient knowledge and adherence to infection prevention behaviors. Conclusions Social proximity between health worker and patients predicted greater knowledge and adherence to infection prevention behaviors but the latter rate remains undesirably low.

Reaction of [Cp*Ir(CH3CN)3][PF6]2 with methylenebis(N-methylimidazolium) iodide in the presence of Et3N affords [Cp*Ir(C−C)I]PF6 (1) (C−C = bis-carbene). The structure of complex 1 was confirmed by X-ray crystallography. The chloride analogue [Cp*Ir(C−C)Cl]X (2) was similarly prepared from [Cp*Ir(CH3CN)3][PF6]2 (X = PF6) or [Cp*IrCl2]2 (X = Cl) and methylenebis(N-methylimidazolium) chloride. Reaction of 2 (X = Cl) with Et3SiB(C6F5)4 under hydrogen gas gives the dicationic dihydrogen complex [Cp*Ir(C−C)(H2)]2+ (3). Complex 3 is identified as a dihydrogen complex based on T1(min) = 37 ms for the hydride resonance (240 K, 750 MHz) and JHD = 23.5 Hz in the partially deuterated analogue.