title: Chronic uranium contamination alters spinal motor neuron integrity via modulation of SMN1 expression and microglia recruitment.
abstract: Consequences of uranium contamination have been extensively studied in brain as cognitive function impairments were observed in rodents. Locomotor disturbances have also been described in contaminated animals. Epidemiological studies have revealed increased risk of motor neuron diseases in veterans potentially exposed to uranium during their military duties. To our knowledge, biological response of spinal cord to uranium contamination has not been studied even though it has a crucial role in locomotion. Four groups of rats were contaminated with increasing concentrations of uranium in their drinking water compared to a control group to study cellular mechanisms involved in locomotor disorders. Nissl staining of spinal cord sections revealed the presence of chromatolytic neurons in the ventral horn. This observation was correlated with a decreased number of motor neurons in the highly contaminated group and a decrease of SMN1 protein expression (Survival of Motor Neuron 1). While contamination impairs motor neuron integrity, an increasing number of microglial cells indicates the trigger of a neuroinflammation process. Potential overexpression of a microglial recruitment chemokine, MCP-1 (Monocyte Chimioattractant Protein 1), by motor neurons themselves could mediate this process. Studies on spinal cord appear to be relevant for risk assessment of population exposed via contaminated food and water.
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire, Pôle Radioprotection de l'Homme, Service de Radiobiologie et d'Epidémiologie, Laboratoire de Radiotoxicologie Expérimentale, BP17, 92262 Fontenay aux Roses, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Saint-Marc
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire, Pôle Radioprotection de l'Homme, Service de Radiobiologie et d'Epidémiologie, Laboratoire de Radiotoxicologie Expérimentale, BP17, 92262 Fontenay aux Roses, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Elie
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire, Pôle Radioprotection de l'Homme, Service de Radiobiologie et d'Epidémiologie, Laboratoire de Radiotoxicologie Expérimentale, BP17, 92262 Fontenay aux Roses, France.
authors.forename: Line
authors.initials: L
authors.lastname: Manens
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire, Pôle Radioprotection de l'Homme, Service de Radiobiologie et d'Epidémiologie, Laboratoire de Radiotoxicologie Expérimentale, BP17, 92262 Fontenay aux Roses, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Tack
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire, Pôle Radioprotection de l'Homme, Service de Radiobiologie et d'Epidémiologie, Laboratoire de Radiotoxicologie Expérimentale, BP17, 92262 Fontenay aux Roses, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Benderitter
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire, Pôle Radioprotection de l'Homme, Service de Radiobiologie et d'Epidémiologie, Laboratoire de Radiotoxicologie Expérimentale, BP17, 92262 Fontenay aux Roses, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Gueguen
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire, Pôle Radioprotection de l'Homme, Service de Radiobiologie et d'Epidémiologie, Laboratoire de Radiotoxicologie Expérimentale, BP17, 92262 Fontenay aux Roses, France. Electronic address: chrystelle.ibanez@irsn.fr.
authors.forename: Chrystelle
authors.initials: C
authors.lastname: Ibanez
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D015536:Down-Regulation; D000075322:Heavy Metal Poisoning; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D019216:Metals, Heavy / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011041:Poisoning / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics / Q000378:metabolism*; D014502:Uranyl Nitrate / Q000378:metabolism / Q000633:toxicity*
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D019216:Metals, Heavy; C526473:Smn1 protein, rat; D055533:Survival of Motor Neuron 1 Protein; D014502:Uranyl Nitrate
keywords: Inflammation; Microglia; Motor neurons; Spinal cord; Uranium