Brain and Nerves

Author: Gianpiero Pescarmona
Date: 25/11/2009


Neuron share many functions with fungal hyphae.


Molecular mechanisms underlying neuronal subtype specification in the cerebellum.

It has been suggested that several bHLH transcription factors participate in glutamatergic vs. GABAergic neuronal subtype specification in the telencephalic neuroepithelium;

  • Neurogenins 1/2 are expressed in the dorsal telencephalon and involved in glutamatergic neuron generation, while
  • MASH1 is expressed in the ventral telencephalon and participates in producing GABAergic neurons
    • Hypoxia alters gene expression in human neuroblastoma cells toward an immature and neural crest-like phenotype. 2002, Proc Natl Acad Sci U S A. 2002 May 14;99(10):7021-6.
    • Insufficient oxygen and nutrient supply often restrain solid tumor growth, and the hypoxia-inducible factors (HIF) 1 alpha and HIF-2 alpha are key transcription regulators of phenotypic adaptation to low oxygen levels. Moreover, mouse gene disruption studies have implicated HIF-2 alpha in embryonic regulation of tyrosine hydroxylase, a hallmark gene of the sympathetic nervous system. Neuroblastoma tumors originate from immature sympathetic cells, and therefore we investigated the effect of hypoxia on the differentiation status of human neuroblastoma cells. Hypoxia stabilized HIF-1 alpha and HIF-2 alpha proteins and activated the expression of known hypoxia-induced genes, such as vascular endothelial growth factor and tyrosine hydroxylase. These changes in gene expression also occurred in hypoxic regions of experimental neuroblastoma xenografts grown in mice. In contrast, hypoxia decreased the expression of several neuronal/neuroendocrine marker genes but induced genes expressed in neural crest sympathetic progenitors, for instance c-kit and Notch-1. Thus, hypoxia apparently causes dedifferentiation both in vitro and in vivo. These findings suggest a novel mechanism for selection of highly malignant tumor cells with stem-cell characteristics.
Wikigenes"NGN1":"NGN2":"NGN3":"MASH1/ASCL1":"GABA A R":"GABA B R":


Stem Cells GABA receptors

GABA and GABA receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca(2+). 2010
FASEB J. 2010 Apr;24(4):1218-28. Epub 2009 Dec 3.

Gamma-amminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system of vertebrates, serves as an autocrine/paracrine signaling molecule during development, modulating a number of calcium (Ca(2+))-dependent processes, including proliferation, migration, and differentiation, acting via 2 types of GABA receptors (GABARs): ionotropic GABARs and metabotropic GABARs. Here, we demonstrate that mouse embryonic stem cells (mESCs), which possess the capacity for virtually unlimited self-renewal and pluripotency, synthesize GABA and express functional GABARs and GABARs, as well as voltage-gated calcium channels (VGCCs), ryanodine receptors (RyRs), and inwardly rectifying potassium (GIRK) channels. On activation, both GABAR types triggered synergistically intracellular calcium rise. Muscimol (a GABAR agonist) induced single Ca(2+) transients involving both VGCC-mediated Ca(2+) influx and intracellular stores, while baclofen (a GABAR agonist) evoked Ca(2+) transients followed by intercellular Ca(2+) waves and oscillations that were resistant to antagonists and entirely dependent on Ca(2+) release from intracellular stores. Prolonged treatment with muscimol slightly inhibited, while baclofen or SR95531 (a GABAR antagonist) significantly facilitated, mESC proliferation. GABAR-specific ligands also induced morphological and gene expression changes indicating a differentiation shift. Our data suggest that the interplay between GABARs and downstream (coupled) effectors differentially modulates mESC proliferation/differentiation through selective activation of second messenger signaling cascades.-Schwirtlich, M., Emri, Z., Antal, K., Máté, Z., Katarova, Z., Szabó, G. GABA and GABA receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca(2+).

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