Modulation of bilirubin neurotoxicity by Mdr1 in a Ugt1a KO mouse model. (CROSBI ID 653367)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa
Podaci o odgovornosti
Bočkor, LUka ; Bortolussi, Giulia ; Zelenka, Jaroslav ; Tiribelli, Claudio ; Vitek, Libor ; Muro, Andrés Fernando
engleski
Modulation of bilirubin neurotoxicity by Mdr1 in a Ugt1a KO mouse model.
Aims: Neonatal jaundice occurs in about 60% of normal newborns during their first week of life due to a combination of pathologic conditions and/or genetic defects, such as the Gilbert and Crigler-Najjar Syndromes. High-unconjugated bilirubin (UCB) levels may cause severe neurological damage and result in death by kernicterus if untreated. The observation that patients with similarly high UCB levels may present different outcome suggested the existence of different mechanisms that modulate bilirubin toxicity. In previous research the Mdr1 protein emerged as one potential transporter of UCB at the blood-brain barrier (BBB). Our aim is to determine the biological role of Mdr1 as a modulator of UCB neurotoxicity. Methods: We crossed Ugt1a1 KO mice with Mdr1a/b KO animals, thus, combining genetically-induced hyperbilirubinemic mice, with the complete absence of the Mdr1 bilirubin transporter. Mice were treated for 10 days with phototherapy (PT). Results: We showed that Mdr1 absence has a strong impact on UCB neurotoxicity in vivo, measured by the reduced survival of Ugt1a1/Mdr1 double mutants. Survival differences were not associated to changes in gross morphology of the cerebellum, the organ most affected by bilirubin-neurotoxicity, suggesting that UCB causes subtle neurological damage in hyperbilirubinemic animals that, indeed, lead to death. Moreover, after phototherapy discontinuation we observed rapid increase in bilirubin levels which was accompanied by a significant upregulation of Mdr1 in the cerebellum
Neonatal jaundice, UCB, neurological damage, blood-brain barrier, Mdr1, Ugt1a1 KO
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Podaci o prilogu
2014.
objavljeno
Podaci o matičnoj publikaciji
Podaci o skupu
9th FENS Forum of Neuroscience
poster
04.07.2014-10.07.2014
Milano, Italija