TY - JOUR
T1 - Cholestasis alters brain lipid and bile acid composition and compromises motor function in neonatal piglets
AU - Henriksen, Nicole Lind
AU - Hansen, Svend Høime
AU - Lycas, Matthew Domenic
AU - Pan, Xiaoyu
AU - Eriksen, Thomas
AU - Johansen, Lars Søndergaard
AU - Sprenger, Richard R
AU - Ejsing, Christer Stenby
AU - Burrin, Douglas G
AU - Skovgaard, Kerstin
AU - Christensen, Vibeke Brix
AU - Thymann, Thomas
AU - Pankratova, Stanislava
N1 - © 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.
PY - 2022/7
Y1 - 2022/7
N2 - Infants with neonatal cholestasis are prone to neurodevelopmental deficits, however, the underlying pathogenesis is unclear. Lipid malabsorption and accumulation of potentially neurotoxic molecules in the blood such as bile acids are important yet relatively unexplored pathways. Here, we developed a translational piglet model to understand how the molecular bile acid and lipid composition of the brain is affected by this disease and relates to motor function. Piglets (8-days old) had bile duct ligation or sham surgery and were fed a formula diet for 3 weeks. Alongside sensory-motor deficits observed in bile duct-ligated animals, we found a shift toward a more hydrophilic and conjugated bile acid profile in the brain. Additionally, comprehensive lipidomics of the cerebellum revealed a decrease in total lipids including phosphatidylinositols and phosphatidylserines and increases in lysophospholipid species. This was paralleled by elevated cerebellar expression of genes related to inflammation and tissue damage albeit without significant impact on the brain transcriptome. This study offers new insights into the developing brain's molecular response to neonatal cholestasis indicating that bile acids and lipids may contribute in mediating motor deficits.
AB - Infants with neonatal cholestasis are prone to neurodevelopmental deficits, however, the underlying pathogenesis is unclear. Lipid malabsorption and accumulation of potentially neurotoxic molecules in the blood such as bile acids are important yet relatively unexplored pathways. Here, we developed a translational piglet model to understand how the molecular bile acid and lipid composition of the brain is affected by this disease and relates to motor function. Piglets (8-days old) had bile duct ligation or sham surgery and were fed a formula diet for 3 weeks. Alongside sensory-motor deficits observed in bile duct-ligated animals, we found a shift toward a more hydrophilic and conjugated bile acid profile in the brain. Additionally, comprehensive lipidomics of the cerebellum revealed a decrease in total lipids including phosphatidylinositols and phosphatidylserines and increases in lysophospholipid species. This was paralleled by elevated cerebellar expression of genes related to inflammation and tissue damage albeit without significant impact on the brain transcriptome. This study offers new insights into the developing brain's molecular response to neonatal cholestasis indicating that bile acids and lipids may contribute in mediating motor deficits.
UR - http://www.scopus.com/inward/record.url?scp=85133997396&partnerID=8YFLogxK
U2 - 10.14814/phy2.15368
DO - 10.14814/phy2.15368
M3 - Journal article
C2 - 35822260
SN - 2051-817X
VL - 10
JO - Physiological Reports
JF - Physiological Reports
IS - 13
M1 - e15368
ER -