Publication Date
7-1-2022
Journal
Physiological Reports
DOI
10.14814/phy2.15368
PMID
35822260
PMCID
PMC9277266
PubMedCentral® Posted Date
7-12-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Animals, Bile Acids and Salts, Bile Ducts, Brain, Cholestasis, Humans, Lipids, Swine, bile acids, brain, cholestasis, lipids, motor skills
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.
Included in
Digestive System Diseases Commons, Gastroenterology Commons, Hepatology Commons, Medical Sciences Commons, Pediatrics Commons