The influence of the Great Recession on perinatal health—an ecological study on the trend changes and regional differences in Portugal

Background: Few studies examine the relationship between socioeconomic factors and trends in mortality in high-income European countries. Due to the lack of regional-level data, most recent studies on social inequality in Portugal do not investigate regional differences. This study analyses time trends and regional disparities in the evolution of perinatal mortality (PMR) and infant mortality (IMR) associated with demographic and socioeconomic indicators following Portugal's 2008 economic and financial crisis. Methods: Associations were assessed using generalised linear models. A Poisson joinpoint regression model was applied to identify relevant PMR and IMR changes between 2000 and 2018. Country regional disparities were analysed using Mixed Effect Multilevel models. Findings: IMR and PMR significantly decreased in the pre-crisis period but not in the post-crisis period. The significant differences between regions in IMR and PMR in 2000 were followed by a different evolution of regional IMR after 2008. PMR and IMR were not significantly associated with socioeconomic indicators. A significant positive association with maternal age at first birth was identified. Interpretation: Results confirm the influence of the crisis on PMR and IMR trends in Portugal, taking into account recurring associations between macroeconomic cycles, variations in mortality trends, macroeconomic volatility, and stagnation of IMR and PMR. Regional inequalities confirm the internal variability of the crisis influence and persistent spatial inequalities affecting IMR patterns. Funding: FCT, under the Institute of Public Health of the University of Porto (ISPUP)– EPIUnit ( UIDB/04750/2020) and ITR ( LA/P/0064/2020), Maastricht University's external PhD programme under the Care and Public Health Research Institute ( CAPHRI), and the RECAP preterm project (grant agreement no 733280). © 2023 The Author(s)FCT, under the Institute of Public Health of the University of Porto (ISPUP)–EPIUnit (UIDB/04750/2020) and ITR (LA/P/0064/2020), Maastricht University's external PhD programme under the Care and Public Health Research Institute (CAPHRI), and the RECAP preterm project (grant agreement no 733280)

In Vivo Fate Analysis Reveals the Multipotent and Self-Renewal Features of Embryonic AspM Expressing Cells

Radial Glia (RG) cells constitute the major population of neural progenitors of the mouse developing brain. These cells are located in the ventricular zone (VZ) of the cerebral cortex and during neurogenesis they support the generation of cortical neurons. Later on, during brain maturation, RG cells give raise to glial cells and supply the adult mouse brain of Neural Stem Cells (NSC). Here we used a novel transgenic mouse line expressing the CreERT2 under the control of AspM promoter to monitor the progeny of an early cohort of RG cells during neurogenesis and in the post natal brain. Long term fate mapping experiments demonstrated that AspM-expressing RG cells are multi-potent, as they can generate neurons, astrocytes and oligodendrocytes of the adult mouse brain. Furthermore, AspM descendants give also rise to proliferating progenitors in germinal niches of both developing and post natal brains. In the latter –i.e. the Sub Ventricular Zone- AspM descendants acquired several feature of neural stem cells, including the capability to generate neurospheres in vitro. We also performed the selective killing of these early progenitors by using a Nestin-GFPflox-TK allele. The forebrain specific loss of early AspM expressing cells caused the elimination of most of the proliferating cells of brain, a severe derangement of the ventricular zone architecture, and the impairment of the cortical lamination. We further demonstrated that AspM is expressed by proliferating cells of the adult mouse SVZ that can generate neuroblasts fated to become olfactory bulb neurons

The Recently Identified P2Y-Like Receptor GPR17 Is a Sensor of Brain Damage and a New Target for Brain Repair

Deciphering the mechanisms regulating the generation of new neurons and new oligodendrocytes, the myelinating cells of the central nervous system, is of paramount importance to address new strategies to replace endogenous damaged cells in the adult brain and foster repair in neurodegenerative diseases. Upon brain injury, the extracellular concentrations of nucleotides and cysteinyl-leukotrienes (cysLTs), two families of endogenous signaling molecules, are markedly increased at the site of damage, suggesting that they may act as “danger signals” to alert responses to tissue damage and start repair. Here we show that, in brain telencephalon, GPR17, a recently deorphanized receptor for both uracil nucleotides and cysLTs (e.g., UDP-glucose and LTD4), is normally present on neurons and on a subset of parenchymal quiescent oligodendrocyte precursor cells. We also show that induction of brain injury using an established focal ischemia model in the rodent induces profound spatiotemporal-dependent changes of GPR17. In the lesioned area, we observed an early and transient up-regulation of GPR17 in neurons expressing the cellular stress marker heat shock protein 70. Magnetic Resonance Imaging in living mice showed that the in vivo pharmacological or biotechnological knock down of GPR17 markedly prevents brain infarct evolution, suggesting GPR17 as a mediator of neuronal death at this early ischemic stage. At later times after ischemia, GPR17 immuno-labeling appeared on microglia/macrophages infiltrating the lesioned area to indicate that GPR17 may also acts as a player in the remodeling of brain circuitries by microglia. At this later stage, parenchymal GPR17+ oligodendrocyte progenitors started proliferating in the peri-injured area, suggesting initiation of remyelination. To confirm a specific role for GPR17 in oligodendrocyte differentiation, the in vitro exposure of cortical pre-oligodendrocytes to the GPR17 endogenous ligands UDP-glucose and LTD4 promoted the expression of myelin basic protein, confirming progression toward mature oligodendrocytes. Thus, GPR17 may act as a “sensor” that is activated upon brain injury on several embryonically distinct cell types, and may play a key role in both inducing neuronal death inside the ischemic core and in orchestrating the local remodeling/repair response. Specifically, we suggest GPR17 as a novel target for therapeutic manipulation to foster repair of demyelinating wounds, the types of lesions that also occur in patients with multiple sclerosis