Anne Gro W. Rognlien
Position: PhD student, MD
Phone: +47 23 07 24 93
Email:

PhD project: Changes in gene-expression with time after hypoxia and reoxygenation


Research group

Anne Gro Wesenberg Rognlien, PFI

Embjørg Wollen, PFI

Monica Atneosen-Aasegg, PFI

Magnar Bjørås, Dept. of  Microbiology (Supervisor)

Ola Didrik Saugstad, PFI (Main supervisor)

 

Background

Asphyxia of the newborn is a major cause of death and disability worldwide. One of the types of injury after asphyxia is hypoxia-reoxygenation (HR) injury. PFI has developed a model where postnatal day 7 mice are subjected to hypoxia and reoxygenation with different FiO2, and we study changes in gene expression (mRNA) and protein concentrations in this model. Ogg1-/-, Mutyh-/- double knockout mice lack two DNA-glycosylases important in initializing the Base excision repair (BER) pathway. The BER pathway repairs oxidative DNA-injury, and Ogg1 and Mutyh repair oxidized Guanine (8-oxoG) lesions to prevent C:G to A:T mutations.

 

Objectives

To study changes with time in the gene expression of 44 a priori selcted genes and the protein concentration of the most interesting genes after hypoxia and reoxygenation in our established mouse model, and to compare the changes in transcription between wild type mice and double knockout Ogg1 -/-, Mutyh -/- mice.

 

Methods

C57BL/6 mice and  Ogg1 -/-, Mutyh -/- mice (postnatal day 7) were randomized to two hours of hypoxia (FiO2 0.08) or air (controls). The hypoxia group was further randomized to 30 min reoxygenation with FiO2 0.60 or air. After observation from 0 h to 3 days, organs were harvested. Homogenate of hippocampus and striatum and homogenate of lung has been analyzed for mRNA expression of 44 genes by real-time RT-PCR in both wild type and knockout mice, and for protein in wild type mice only.


Results and conclusions

Hyperoxic reoxygenation after hypoxia gives a stronger response in inflammatory genes (Cxcl10, Hmox1, Il1b, Nfkb1and Tgfb1) and less suppression of the DNA glycosylase Neil3 in wild type mice. Also, we identified three patterns of gene expression changes after hypoxia regardless of reoxygenation mode. The results from lung tissue and knockout mice are not yet published.

 

Financial Support

The Norwegian Research Council; The Laerdal Foundation; The Norwegian SIDS and Stillbirth Society; Renée og Bredo Grimsgaard's Stiftelse; Kvinne- og Barneklinikkens FU-fond; and Skibsreder Tom Wilhelmsens Stiftelse.

 

Publications

Rognlien AGW, Wollen E, Atnesen-Åsegg M, Saugstad OD: Increased expression of inflammatory genes in the neonatal mouse brain after hyperoxic reoxygenation (Submitted manuscript).

 

Presentations

Gene expression changes in the brain of Ogg1/Mutyh knockout mice following a hypoxia-reoxygenation insult. Poster at the European Society of Pediatric Research meeting, Porto 2013.

DNA glycosylases protect the newborn mouse lung from apoptosis, cell cycle arrest and inflammation. 28th International Workshop on surfactant replacement, June 1st 2013, Helsinki, Finland. (Oral presentation).

 

Author network for Anne Gro Wesenberg Rognlien by COREMINE medical


Publications 2016

Rognlien AG, Wollen EJ, Atneosen-Åsegg M, Saugstad OD (2016)
Temporal Patterns of Gene Expression Profiles in the Neonatal Mouse Lung after Hypoxia-Reoxygenation
Neonatology, 111 (1), 45-54
PubMed 27529351

Publications 2014

Rognlien AG, Wollen EJ, Atneosen-Åsegg M, Saugstad OD (2014)
Increased expression of inflammatory genes in the neonatal mouse brain after hyperoxic reoxygenation
Pediatr Res, 77 (2), 326-33
PubMed 25423075

Publications 2011

Kristoffersen AW, Nordbø SA, Rognlien AG, Christensen A, Døllner H (2011)
Coronavirus causes lower respiratory tract infections less frequently than RSV in hospitalized Norwegian children
Pediatr Infect Dis J, 30 (4), 279-83
PubMed 21057374

Publications 2010

Christensen A, Nordbø SA, Krokstad S, Rognlien AG, Døllner H (2010)
Human bocavirus in children: mono-detection, high viral load and viraemia are associated with respiratory tract infection
J Clin Virol, 49 (3), 158-62
PubMed 20833582

Publications 2009

Flem E, Vainio K, Døllner H, Midgaard C, Bosse FJ, Rognlien AG, Rojahn A, Nordbo SA, Størvold G, Njølstad G, Wathne KO, Konsmo K, Aavitsland P (2009)
Rotavirus gastroenteritis in Norway: analysis of prospective surveillance and hospital registry data
Scand J Infect Dis, 41 (10), 753-9
PubMed 19685376

Vainio K, Nordbø SA, Njølstad G, Størvold G, Døllner H, Midgaard C, Bosse FJ, Rognlien AG, Rojahn A, Wathne KO, Flem E (2009)
Detection and characterization of group A rotaviruses in children hospitalized with acute gastroenteritis in Norway, 2006-2008
J Med Virol, 81 (10), 1839-44
PubMed 19697411

Publications 2008

Christensen A, Nordbø SA, Krokstad S, Rognlien AG, Døllner H (2008)
Human bocavirus commonly involved in multiple viral airway infections
J Clin Virol, 41 (1), 34-7
PubMed 18069054