Search results for "Brain."
showing 10 items of 3987 documents
Design, synthesis and biological evaluation of new anticancer drugs: FGFR inhibitors
2021
Fibroblast growth factor receptors (FGFRs) constitute a family of tyrosine kinases receptors (RTKs) that exert pivotal physiological functions in human embryonic and adult tissues. Hyperactivated FGFR signaling drives tumorigenesis in multiple cancer types, including lung and brain cancers. Great effort has been laid on the development of new compounds that specifically target the FGFR axis. However, cancer cell- based and microenvironmental resistance mechanisms against FGFR inhibitors often arise and are currently poorly understood. Furthermore, FGFR-targeted therapy often presents different side effects, e due to the broad biological spectrum of the FGFR signaling axis as well as to its …
Postpleistocene evolution of the brain?
1976
The number of extraneurons (Nc) has been calculated with the formulae of Jerison ('63) for prehistoric population samples to check the hypothesis that Nc may not only increase by increasing of cranial capacity but also by decreasing of body-weight (gracilisation). Body weight of skeletal populations has been estimated by the formula of Debetz ('67). Samples from the Western part of Europe and Egypt support the hypothesis, but Eastern europoid samples display opposite relations: Nc increases with robusticity. It seems (as Jerison already suggested) that Nc is no measurement of the level of behavior in the populations of H. sapiens; but it may point towards allometric differences between West…
Persistent inflammation alters the function of the endogenous brain stem cell compartment
2008
Endogenous neural stem/precursor cells (NPCs) are considered a functional reservoir for promoting tissue homeostasis and repair after injury, therefore regenerative strategies that mobilize these cells have recently been proposed. Despite evidence of increased neurogenesis upon acute inflammatory insults (e.g. ischaemic stroke), the plasticity of the endogenous brain stem cell compartment in chronic CNS inflammatory disorders remains poorly characterized. Here we show that persistent brain inflammation, induced by immune cells targeting myelin, extensively alters the proliferative and migratory properties of subventricular zone (SVZ)-resident NPCs in vivo leading to significant accumulation…
Differential diurnal variations of anandamide and 2-arachidonoyl-glycerol levels in rat brain.
2004
The endogenous ligands of cannabinoid receptors, also known as endocannabinoids, have been implicated in many physiological and pathological processes of the central nervous system. Here we show that the levels of the two major endocannabinoids, anandamide and 2-arachidonoyl-glycerol (2-AG), in four areas of the rat brain, change dramatically between the light and dark phases of the day. While anandamide levels in the nucleus accumbens, pre-frontal cortex, striatum and hippocampus were significantly higher in the dark phase, the opposite was observed with 2-AG, whose levels were significantly higher during the light phase in all four regions. We found that the activity of the fatty acid ami…
Phenotypic analysis of individuals with Costello syndrome due to HRAS p.G13C.
2011
Costello syndrome is characterized by severe failure-to-thrive, short stature, cardiac abnormalities (heart defects, tachyarrhythmia, and hypertrophic cardiomyopathy (HCM)), distinctive facial features, a predisposition to papillomata and malignant tumors, postnatal cerebellar overgrowth resulting in Chiari 1 malformation, and cognitive disabilities. De novo germline mutations in the proto-oncogene HRAS cause Costello syndrome. Most mutations affect the glycine residues in position 12 or 13, and more than 80% of patients share p.G12S. To test the hypothesis that subtle genotype-phenotype differences exist, we report the first cohort comparison between 12 Costello syndrome individuals with p…
Novel Approaches for Glioblastoma Treatment: Focus on Tumor Heterogeneity, Treatment Resistance, and Computational Tools
2019
BACKGROUND: Glioblastoma (GBM) is a highly aggressive primary brain tumor. Currently, the suggested line of action is the surgical resection followed by radiotherapy and treatment with the adjuvant temozolomide (TMZ), a DNA alkylating agent. However, the ability of tumor cells to deeply infiltrate the surrounding tissue makes complete resection quite impossible, and in consequence, the probability of tumor recurrence is high, and the prognosis is not positive. GBM is highly heterogeneous and adapts to treatment in most individuals. Nevertheless, these mechanisms of adaption are unknown. RECENT FINDINGS: In this review, we will discuss the recent discoveries in molecular and cellular heterog…
Transient oligemia is associated with long-term changes in binding densities of cortical inhibitory GABAA receptors in the rat brain
2009
Recently, we could demonstrate in rats that a short transient oligemic period of only 20-minute duration, induced by systemic hypotension, resulted in a transient decline of spatial memory capacities without any histological damage over a subsequent period of 6 months. In our present study, we checked for more subtle alterations within the highly vulnerable hippocampal CA1 subfield using quantification of neuronal cell density and semi-quantitative analysis of the ischemia-sensitive protein MAP2. Since hippocampal excitatory and inhibitory neurotransmitter receptors are crucially involved in spatial memory processes, quantitative in vitro receptor autoradiography was performed using [(3)H]M…
Neurovascular EGFL7 regulates adult neurogenesis in the subventricular zone and thereby affects olfactory perception
2016
Adult neural stem cells reside in a specialized niche in the subventricular zone (SVZ). Throughout life they give rise to adult-born neurons in the olfactory bulb (OB), thus contributing to neural plasticity and pattern discrimination. Here, we show that the neurovascular protein EGFL7 is secreted by endothelial cells and neural stem cells (NSCs) of the SVZ to shape the vascular stem-cell niche. Loss of EGFL7 causes an accumulation of activated NSCs, which display enhanced activity and re-entry into the cell cycle. EGFL7 pushes activated NSCs towards quiescence and neuronal progeny towards differentiation. This is achieved by promoting Dll4-induced Notch signalling at the blood vessel-stem …
Dissociable contributions of left and right dorsolateral prefrontal cortex in planning.
2010
It is well established that the mid-dorsolateral prefrontal cortex (dlPFC) plays a critical role in planning. Neuroimaging studies have yielded predominantly bilateral dlPFC activations, but the existence and nature of functionally specific contributions of left and right dlPFC have remained elusive. In recent experiments, 2 independent parameters have been identified which substantially determine planning: 1) the degree of interdependence between consecutive steps (search depth) and 2) the degree to which the configuration of the goal state renders the order of single steps either clearly evident or ambiguous (goal hierarchy). Thus, search depth affects the actual mental generation and eva…
Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety,…
2011
Intensive research is devoted to unravel the neurobiological mechanisms mediating adult hippocampal neurogenesis, its regulation by antidepressants, and its behavioral consequences. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that is expressed in the CNS, where its function is unknown. Here, we show, for the first time, the relevance of MIF expression for adult hippocampal neurogenesis. We identify MIF expression in neurogenic cells (in stem cells, cells undergoing proliferation, and in newly proliferated cells undergoing maturation) in the subgranular zone of the rodent dentate gyrus. A causal function for MIF in cell proliferation was shown using genetic (M…