title: Why do premature newborn infants display elevated blood adenosine levels?
abstract: Our preliminary data show high levels of adenosine in the blood of very low birth weight (VLBW) infants, positively correlating to their prematurity (i.e. body weight class). This prompted us to look for a mechanism promoting such impressive adenosine increase. We hypothesized a correlation with oxygen challenge. In fact, it is recognized that either oxygen lack or its excess contribute to the pathogenesis of the injuries of prematurity, such as retinopathy (ROP) and periventricular white matter lesions (PWMI). The optimal concentration of oxygen for resuscitation of VLBW infants is currently under revision. We propose that the elevated adenosine blood concentrations of VLBW infants recognizes two sources. The first could be its activity-dependent release from unmyelinated brain axons. Adenosine in this respect would be an end-product of the hypometabolic VLBW newborn unmyelinated axon intensely firing in response to the environmental stimuli consequent to premature birth. Adenosine would be eventually found in the blood due to blood-brain barrier immaturity. In fact, adenosine is the primary activity-dependent signal promoting differentiation of premyelinating oligodendrocyte progenitor cells (OPC) into myelinating cells in the Central Nervous System, while inhibiting their proliferation and inhibiting synaptic function. The second, would be the ecto-cellular ATP synthesized by the endothelial cell plasmalemma exposed to ambient oxygen concentrations due to premature breathing, especially in lung. ATP would be rapidly transformed into adenosine by the ectonucleotidase activities such as NTPDase I (CD39), and NT5E (CD73). An ectopic extra-mitochondrial aerobic ATP synthetic ability was reported in many cell plasma-membranes, among which endothelial cells. The potential implications of the cited hypotheses for the neonatology area would be great. The amount of oxygen administration for reviving of newborns would find a molecular basis for its assessment. VLBW infants may be regarded as those in which premature exposure to ambient oxygen concentrations and oxidative stress causes a premature functioning of the extra-mitochondrial oxidative phosphorylation primarily in axons and endothelium. Adenosine may become a biomarker of prematurity risk, whose implications further studies may assess.
authors.affiliation: Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy. Electronic address: Isabella.Panfoli@unige.it.
authors.forename: Isabella
authors.initials: I
authors.lastname: Panfoli
authors.affiliation: Neonatal Intensive Care Unit, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Cassanello
authors.affiliation: Institute for Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bruschettini
authors.affiliation: Neonatal Intensive Care Unit, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Colella
authors.affiliation: U.O.S. Malattie Metaboliche, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cerone
authors.affiliation: Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ravera
authors.affiliation: Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Calzia
authors.affiliation: Laboratory of Pathophysiology of Uremia, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Candiano
authors.affiliation: Neonatal Intensive Care Unit, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Ramenghi
mesh_terms: D000200:Action Potentials; D000241:Adenosine / Q000097:blood*; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D001369:Axons / Q000378:metabolism; D001812:Blood-Brain Barrier; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood*; D019102:Infant, Very Low Birth Weight / Q000097:blood*; D008954:Models, Biological; D009186:Myelin Sheath / Q000502:physiology; D055495:Neurogenesis; D009836:Oligodendroglia / Q000166:cytology; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D010100:Oxygen / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D010102:Oxygen Inhalation Therapy / Q000009:adverse effects
chemical_list: D000255:Adenosine Triphosphate; D000241:Adenosine; D010100:Oxygen