Biomedical subjects

Vittorio Gallo

Publications and source records attributed to Vittorio Gallo.

22 records · Page 2Linked to original sources

PubMed2002

Adenosine: a neuron-glial transmitter promoting myelination in the CNS in response to action potentials.

Neuronal activity influences myelination of the brain, but the molecular mechanisms involved are largely unknown. Here, we report that oligodendrocyte progenitor cells (OPCs) express functional adenosine receptors, which are activated in response to action potential firing. Adenosine acts as a potent neuron-glial transmitter to inhibit OPC proliferation, stimulate differentiation, and promote the formation of myelin. This neuron-glial signal provides a molecular mechanism for promoting oligodendrocyte development and myelination in response to impulse activity and may help resolve controversy on the opposite effects of impulse activity on myelination in the central and peripheral nervous systems.

Action Potentials↗

PubMed2002

Expression of the green fluorescent protein in the oligodendrocyte lineage: a transgenic mouse for developmental and physiological studies.

We generated a transgenic mouse expressing the enhanced green fluorescent protein (EGFP) under the control of the 2'-3'-cyclic nucleotide 3'-phosphodiesterase (CNP) promoter. EGFP(+) cells were visualized in live tissue throughout embryonic and postnatal development. Immunohistochemical analysis in brain tissue and in sciatic nerve demonstrated that EGFP expression was restricted to cells of the oligodendrocyte and Schwann cell lineages. EGFP was also strongly expressed in "adult" oligodendrocyte progenitors (OPs) and in gray matter oligodendrocytes. Fluorescence-activated cell sorting allowed high-yield purification of EGFP(+) oligodendrocyte-lineage cells from transgenic brains. Electrophysiological patch clamp recordings of EGFP(+) cells in situ demonstrated that OP cells displayed large outward tetraethylammonium (TEA)-sensitive K(+) currents and very small inward currents, whereas mature oligodendrocytes were characterized by expression of large inward currents and small outward K(+) currents. The proliferation rate of EGFP(+) cells in developing white matter decreased with the age of the animals and was strongly inhibited by TEA. Oligodendrocyte development and physiology can be studied in live tissue of CNP-EGFP transgenic mice, which represent a source of pure EGFP(+) oligodendrocyte-lineage cells throughout development.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

PubMed2002

Cyclin-dependent kinase-2 controls oligodendrocyte progenitor cell cycle progression and is downregulated in adult oligodendrocyte progenitors.

Proliferation of oligodendrocyte progenitor (OP) cells is a crucial process controlling myelination in the CNS. Previous studies demonstrated a correlation between OP proliferation rate and cyclin E/cyclin-dependent kinase-2 (cdk2) activity. To establish a causal link between cyclin E/cdk2 activity and OP proliferation, we selectively modulated cdk2 activity in vitro by transfection of cultured OP cells. Dominant-negative (Dn)-cdk2 overexpression inhibited mitogen-induced OP cell proliferation, whereas wild-type (wt)-cdk2 prevented cell cycle arrest caused by anti-mitotic signals. Dn-cdk2- or wt-cdk2-mediated regulation of G(1)/S transition, per se, did not influence initiation of OP differentiation. To study the function of cyclin E/cdk2 in OP cells during development in vivo, we analyzed cdk2 and cyclin E expression in cells acutely isolated from transgenic mice expressing the green fluorescent protein (GFP) under the control of the 2'-3'-cyclic nucleotide 3'-phosphodiesterase gene promoter. Both cyclin E/cdk2 protein levels and activity were decreased in GFP(+) oligodendrocyte lineage cells between postnatal days 4 and 30. Immunostaining of NG2(+)/GFP(+) OP cells in brain tissue sections showed a 90% decrease in overall cell proliferation and cdk2 expression between perinatal and adult cells. However, cdk2 expression within the proliferating (i.e., expressing the proliferating cell nuclear antigen) OP cell population was maintained throughout development. Our data indicate that: (1) cyclin E/cdk2 activity plays a pivotal function in OP cell cycle decisions occurring at G(1)/S checkpoint; (2) initiation of OP differentiation is independent of cyclinE/cdk2 checkpoint, and (3) intrinsic differences in cyclin E/cdk2 expression and activity may underlie the slowly proliferative state that characterizes so-called "quiescent" adult OP cells in vivo.

Animals↗

PubMed2002

Brain development and the ontogeny of developmental disabilities.

Brain development is an active process that continues throughout life. During the past few decades, increased knowledge of this process has led to an improved understanding of the causes of its disruption. Complex genetic and molecular processes have been identified as components of the sequence of events leading to mature brain formation. However, the limitations in our knowledge about brain development are still significant. For example, 10% to 20% of persons with severe mental retardation of unknown origin appear entirely normal by standard neuropathologic studies. In this chapter, we review normal brain development and discuss how alterations during this process can lead to developmental disabilities. An overview of the most important steps in brain development, the basic mechanisms involved, and possible etiologies for the clinical manifestations of developmental disabilities is provided. General concepts about brain development, timing, and environmental influences are also considered. As we learn more about the genetic mechanism and molecular processes underlying brain development, we will better understand the ontogeny of various developmental disabilities and hopefully improve approaches to prevention and treatment.

Brain Chemistry↗