Search results for "pathways"
showing 10 items of 644 documents
Oligodendroglial p130Cas Is a Target of Fyn Kinase Involved in Process Formation, Cell Migration and Survival
2014
Oligodendrocytes are the myelinating glial cells of the central nervous system. In the course of brain development, oligodendrocyte precursor cells migrate, scan the environment and differentiate into mature oligodendrocytes with multiple cellular processes which recognize and ensheath neuronal axons. During differentiation, oligodendrocytes undergo dramatic morphological changes requiring cytoskeletal rearrangements which need to be tightly regulated. The non-receptor tyrosine kinase Fyn plays a central role in oligodendrocyte differentiation and myelination. In order to improve our understanding of the role of oligodendroglial Fyn kinase, we have identified Fyn targets in these cells. Pur…
Quinoline-Based Molecules Targeting c-Met, EGF, and VEGF Receptors and the Proteins Involved in Related Carcinogenic Pathways
2020
The quinoline ring system has long been known as a versatile nucleus in the design and synthesis of biologically active compounds. Currently, more than one hundred quinoline compounds have been approved in therapy as antimicrobial, local anaesthetic, antipsychotic, and anticancer drugs. In drug discovery, indeed, over the last few years, an increase in the publication of papers and patents about quinoline derivatives possessing antiproliferative properties has been observed. This trend can be justified by the versatility and accessibility of the quinoline scaffold, from which new derivatives can be easily designed and synthesized. Within the numerous quinoline small molecules developed as a…
Novel [1,2,3]triazolo[1,5-a]pyridine derivatives are trypanocidal by sterol biosynthesis pathway alteration.
2019
Aim: To study a new series of [1,2,3]triazolo[1,5-α]pyridine derivatives as trypanocidal agents because current antichagasic pharmacologic therapy is only partially effective. Materials & methods: The effect of the series upon Trypanosoma cruzi epimastigotes and murine macrophages viability, cell cycle, cell death and on the metabolites of the sterol biosynthesis pathway was measured; also, docking in 14α-demethylase was analyzed. Results: Compound 16 inhibits 14α-demethylase producing an imbalance in the cholesterol/ergosterol synthesis pathway, as suggested by a metabolic control and theoretical docking analysis. Consequently, it prevented cell proliferation, stopping the cellular cy…
Compartmentalization of Central Neurons inDrosophila: A New Strategy of Mosaic Analysis Reveals Localization of Presynaptic Sites to Specific Segment…
2002
Synaptogenesis in the CNS has received far less attention than the development of neuromuscular synapses, although only central synapses allow the study of neuronal postsynaptic mechanisms and display a greater variety of structural and functional features. This neglect is attributable mainly to the enormous complexity of the CNS, which makes the visualization of individual synapses on defined neuronal processes very difficult. We overcome this obstacle and demonstrate by confocal microscopy the specific arrangement of output synapses on individual neurites. These studies are performed via genetic mosaic strategies in the CNS of the fruitfly Drosophila melanogaster. First, we use targeted e…
Polysialic acid is required for dopamine D2 receptor-mediated plasticity involving inhibitory circuits of the rat medial prefrontal cortex.
2011
Decreased expression of dopamine D2 receptors (D2R), dysfunction of inhibitory neurotransmission and impairments in the structure and connectivity of neurons in the medial prefrontal cortex (mPFC) are involved in the pathogenesis of schizophrenia and major depression, but the relationship between these changes remains unclear. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-related molecule, may serve as a link. This molecule is expressed in cortical interneurons and dopamine, via D2R, modulates its expression in parallel to that of proteins related to synapses and inhibitory neurotransmission, suggesting that D2R-targeted antipsychotics/antidepressants…
Morphological Characterization of the Entire Interneuron Population Reveals Principles of Neuromere Organization in the Ventral Nerve Cord ofDrosophi…
2011
Decisive contributions to our understanding of the mechanisms underlying the development of the nervous system have been made by studies performed at the level of single, identified cells in the fruit flyDrosophila. While all the motor neurons and glial cells in thoracic and abdominal segments of theDrosophilaembryo have been individually identified, few of the interneurons, which comprise the vast majority of cells in the CNS, have been characterized at this level. We have applied a single cell labeling technique to carry out a detailed morphological characterization of the entire population of interneurons in abdominal segments A1–A7. Based on the definition of a set of spatial parameters…
Neuronal Activity Drives Localized Blood-Brain-Barrier Transport of Serum Insulin-like Growth Factor-I into the CNS
2010
Upon entry into the central nervous system (CNS), serum insulin-like growth factor-1 (IGF-I) modulates neuronal growth, survival, and excitability. Yet mechanisms that trigger IGF-I entry across the blood-brain barrier remain unclear. We show that neuronal activity elicited by electrical, sensory, or behavioral stimulation increases IGF-I input in activated regions. Entrance of serum IGF-I is triggered by diffusible messengers (i.e., ATP, arachidonic acid derivatives) released during neurovascular coupling. These messengers stimulate matrix metalloproteinase-9, leading to cleavage of the IGF binding protein-3 (IGFBP-3). Cleavage of IGFBP-3 allows the passage of serum IGF-I into the CNS thro…
Computation of inverse functions in a model of cerebellar and reflex pathways allows to control a mobile mechanical segment.
2003
Abstract The command and control of limb movements by the cerebellar and reflex pathways are modeled by means of a circuit whose structure is deduced from functional constraints. One constraint is that fast limb movements must be accurate although they cannot be continuously controlled in closed loop by use of sensory signals. Thus, the pathways which process the motor orders must contain approximate inverse functions of the bio-mechanical functions of the limb and of the muscles. This can be achieved by means of parallel feedback loops, whose pattern turns out to be comparable to the anatomy of the cerebellar pathways. They contain neural networks able to anticipate the motor consequences …
Electrophysiological Investigations of Retinogeniculate and Corticogeniculate Synapse Function
2019
The lateral geniculate nucleus is the first relay station for the visual information. Relay neurons of this thalamic nucleus integrate input from retinal ganglion cells and project it to the visual cortex. In addition, relay neurons receive top-down excitation from the cortex. The two main excitatory inputs to the relay neurons differ in several aspects. Each relay neuron receives input from only a few retinogeniculate synapses, which are large terminals with many release sites. This is reflected by the comparably strong excitation, the relay neurons receive, from retinal ganglion cells. Corticogeniculate synapses, in contrast, are simpler with few release sites and weaker synaptic strength…
Cortical Temperature Change: A Tool for Modulating Brain States?12
2016
Reduction in temperature depolarizes neurons by a partial closure of potassium channels but decreases the vesicle release probability within synapses. Compared with cooling, neuromodulators produce qualitatively similar effects on intrinsic neuronal properties and synapses in the cortex. We used this similarity of neuronal action in ketamine-xylazine-anesthetized mice and non-anesthetized mice to manipulate the thalamocortical activity. We recorded cortical electroencephalogram/local field potential (LFP) activity and intracellular activities from the somatosensory thalamus in control conditions, during cortical cooling and on rewarming. In the deeply anesthetized mice, moderate cortical co…