Business model analysis of low-cost carriers on the exaple of Ryanair

nicht vorhande

Microglia maintain structural integrity during fetal brain morphogenesis

Microglia (MG), the brain-resident macrophages, play major roles in health and disease via a diversity of cellular states. While embryonic MG display a large heterogeneity of cellular distribution and transcriptomic states, their functions remain poorly characterized. Here, we uncovered a role for MG in the maintenance of structural integrity at two fetal cortical boundaries. At these boundaries between structures that grow in distinct directions, embryonic MG accumulate, display a state resembling post-natal axon-tract-associated microglia (ATM) and prevent the progression of microcavities into large cavitary lesions, in part via a mechanism involving the ATM-factor Spp1. MG and Spp1 furthermore contribute to the rapid repair of lesions, collectively highlighting protective functions that preserve the fetal brain from physiological morphogenetic stress and injury. Our study thus highlights key major roles for embryonic MG and Spp1 in maintaining structural integrity during morphogenesis, with major implications for our understanding of MG functions and brain development.</p

Gliogenèse dans l'hypothalamus au cours du développement postnatal (implication dans le contrôle de la maturation sexuelle femelle)

Notre travail propose de déterminer l'implication de la néogenèse postnatale dans la maturation des neurones hypothalamiques à GnRH, nécessaires à l'initiation de la puberté. Un nombre important de cellules prolifératives est observé dans l'hypothalamus postnatal à différents intervalles de temps après injection de BrdU. 25% des corps cellulaires à GnRH sont morphologiquement associés avec des cellules différentiées générées à P8. Par ailleurs, le nombre de ces cellules BrdU+ double entre P8 et P15. Cette vague de néogenèse précède et accompagne la première activation centrale de l'axe reproducteur. De plus, les cellules nouvellement générées se différencieraient en astrocytes plutôt qu'en neurones. Des expériences de neurosphères in vitro suggèrent la présence de cellules progénitrices multipotentes dans l'hypothalamus. Ces résultats montrent l'existence d'une néogenèse dans l'hypothalamus postnatal et suggèrent que la genèse de nouvelles cellules favorise l'initiation la puberté.The initiation of mammalian puberty requires an increased pulsatile secretion of GnRH from specialized neurons of the hypothalamus controlling sexual development. We have identified newborn cells by injecting BrdU at various intervals thereafter. We report that during sexual maturation a host of new cells is generated in the hypothalamus. This wave of cell neogenesis precedes and accompanies the first gonadal independent GnRH-driven activation of the reproductive axis. By P15 a significant fraction of GnRH neuronal cell bodies is morphologically associated with differentiated cells that were born on P8. Moreover, upto 35% of the cells closely associated with GnRH axon terminals entering cell cycle remain associated with this neurosecretory system once differenciated. These results raise the exciting possibility that birth of new cells is a component of the maturational process required for the activation of GnRH neuronal function at the onset of puberty.LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

EEG alpha band synchrony predicts cognitive and motor performance in patients with ischemic stroke

Functional brain networks are known to be affected by focal brain lesions. However, the clinical relevance of these changes remains unclear. This study assesses resting-state functional connectivity (FC) with electroencephalography (EEG) and relates observed topography of FC to cognitive and motor deficits in patients three months after ischemic stroke. Twenty patients (mean age 61.3 years, range 37-80, 9 females) and nineteen age-matched healthy participants (mean age 66.7 years, range 36-88, 13 females) underwent a ten-minute EEG-resting state examination. The neural oscillations at each grey matter voxel were reconstructed using an adaptive spatial filter and imaginary component of coherence (IC) was calculated as an index of FC. Maps representing mean connectivity value at each voxel were correlated with the clinical data. Compared to healthy controls, alpha band IC of stroke patients was locally reduced in brain regions critical to observed behavioral deficits. A voxel-wise Pearson correlation of clinical performances with FC yielded maps of the neural structures implicated in motor, language, and executive function. This correlation was again specific to alpha band coherence. Ischemic lesions decrease the synchrony of alpha band oscillations between affected brain regions and the rest of the brain. This decrease is linearly related to cognitive and motor deficits observed in the patients

Differential erbB signaling in astrocytes from the cerebral cortex and the hypothalamus of the human brain.: ErbB signaling in human astrocytes

International audienceStudies in rodents have shown that astroglial erbB tyrosine kinase receptors are key regulatory elements in neuron-glia communication. Although both astrocytes and deregulation of erbB functions have been implicated in the pathogenesis of many common human brain disorders, erbB signaling in native human brain astrocytes has never been explored. Taking advantage of our ability to perform primary cultures from the cortex and the hypothalamus of human fetuses, we conducted a thorough analysis of erbB signaling in human astrocytes. We showed that human cortical astrocytes express erbB1, erbB2, and erbB3, whereas human hypothalamic astrocytes express erbB1, erbB2, and erbB4 receptors. Ligand-dependent activation of different erbB receptor heterodimeric complexes in these two populations of astrocytes translated into different morphological and proliferative responses. Although morphological plasticity was more pronounced in hypothalamic astrocytes than in cortical astrocytes, the former showed a lower mitogenic potential. Decreasing erbB4 expression via siRNA-mediated gene knockdown revealed that erbB4 constitutively restrains basal proliferative activity in hypothalamic astrocytes. We further show that treatment of human astrocytes with a protein kinase C activator results in rapid tyrosine phosphorylation of erbB receptors that involves cleavage of endogenous membrane bound erbB ligands by metalloproteinases. Together, these results indicate that erbB signaling in primary human brain astrocytes is functional, region-specific, and can be activated in a paracrine and/or autocrine manner. In addition, by revealing that some aspects of astroglial erbB signaling are different between human and rodents, our results provide a molecular framework to explore the potential involvement of astroglial erbB signaling deregulation in human brain disorders

The behavioral significance of coherent resting-state oscillations after stroke

Stroke lesions induce not only loss of local neural function, but disruptions in spatially distributed areas. However, it is unknown whether they affect the synchrony of electrical oscillations in neural networks and if changes in network coherence are associated with neurological deficits. This study assessed these questions in a population of patients with subacute, unilateral, ischemic stroke. Spontaneous cortical oscillations were reconstructed from high-resolution electroencephalograms (EEG) with adaptive spatial filters. Maps of functional connectivity (FC) between brain areas were created and correlated with patient performance in motor and cognitive scores. In comparison to age matched healthy controls, stroke patients showed a selective disruption of FC in the alpha frequency range. The spatial distribution of alpha band FC reflected the pattern of motor and cognitive deficits of the individual patient: network nodes that participate normally in the affected functions showed local decreases in FC with the rest of the brain. Interregional FC in the alpha band, but not in delta, theta, or beta frequencies, was highly correlated with motor and cognitive performance. In contrast, FC between contralesional areas and the rest of the brain was negatively associated with patient performance. Alpha oscillation synchrony at rest is a unique and specific marker of network function and linearly associated with behavioral performance. Maps of alpha synchrony computed from a single resting-state EEG recording provide a robust and convenient window into the functionality and organization of cortical networks with numerous potential applications

GnRH neurons recruit astrocytes in infancy to facilitate network integration and sexual maturation.

peer reviewedNeurons that produce gonadotropin-releasing hormone (GnRH), which control fertility, complete their nose-to-brain migration by birth. However, their function depends on integration within a complex neuroglial network during postnatal development. Here, we show that rodent GnRH neurons use a prostaglandin D(2) receptor DP1 signaling mechanism during infancy to recruit newborn astrocytes that 'escort' them into adulthood, and that the impairment of postnatal hypothalamic gliogenesis markedly alters sexual maturation by preventing this recruitment, a process mimicked by the endocrine disruptor bisphenol A. Inhibition of DP1 signaling in the infantile preoptic region, where GnRH cell bodies reside, disrupts the correct wiring and firing of GnRH neurons, alters minipuberty or the first activation of the hypothalamic-pituitary-gonadal axis during infancy, and delays the timely acquisition of reproductive capacity. These findings uncover a previously unknown neuron-to-neural-progenitor communication pathway and demonstrate that postnatal astrogenesis is a basic component of a complex set of mechanisms used by the neuroendocrine brain to control sexual maturation