Naslov
Modulation of bilirubin neurotoxicity by Mdr1 in a Ugt1a KO mouse model.

Autori
Bočkor, LUka ; Bortolussi, Giulia ; Zelenka, Jaroslav ; Tiribelli, Claudio ; Vitek, Libor ; Muro, Andrés Fernando

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Skup
9th FENS Forum of Neuroscience

Mjesto i datum
Milano, Italija, 05.07.2014. - 09.07.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
Neonatal jaundice, UCB, neurological damage, blood-brain barrier, Mdr1, Ugt1a1 KO

Sažetak
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

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

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