Cholestasis alters brain lipid and bile acid composition and compromises motor function in neonatal piglets. Issue 13 (12th July 2022)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Physiological reports. Volume 10:Issue 13(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-07-12
• Subjects: bile acids -- brain -- cholestasis -- lipids -- motor skills; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.15368
• Languages: English
• ISSNs: 2051-817X

Abstract

Abstract: 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. Abstract : The underlying pathophysiological processes in cholestasis‐induced neurodevelopmental impairments are unclear. Using a bile duct ligation piglet model, this research demonstrates that neonatal cholestasis induces significant molecular changes in the developing brain related to bile acid and lipid composition and that these findings are paralleled by sensory‐motor deficits.