Open AccessCholestasis alters brain lipid and bile acid composition and compromises motor function in neonatal piglets
Author(s) -
Henriksen Nicole Lind,
Hansen Svend Høime,
Lycas Matthew Domenic,
Pan Xiaoyu,
Eriksen Thomas,
Johansen Lars Søndergaard,
Sprenger Richard R.,
Ejsing Christer Stenby,
Burrin Douglas G.,
Skovgaard Kerstin,
Christensen Vibeke Brix,
Thymann Thomas,
Pankratova Stanislava
Publication year - 2022
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.15368
Subject(s) - cholestasis , bile acid , neonatal cholestasis , medicine , lipidomics , bile duct , endocrinology , cholesterol , biochemistry , biology , chemistry , biliary atresia , transplantation , liver transplantation
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.