Cholestasis alters brain lipid and bile acid composition and compromises motor function in neonatal piglets

Research output: Contribution to journal › Journal article › Research › peer-review

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Cholestasis alters brain lipid and bile acid composition and compromises motor function in neonatal piglets. / 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.

In: Physiological Reports, Vol. 10, No. 13, e15368, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Henriksen, NL, Hansen, SH, Lycas, MD, Pan, X, Eriksen, T, Johansen, LS, Sprenger, RR, Ejsing, CS, Burrin, DG, Skovgaard, K, Christensen, VB, Thymann, T & Pankratova, S 2022, 'Cholestasis alters brain lipid and bile acid composition and compromises motor function in neonatal piglets', Physiological Reports, vol. 10, no. 13, e15368. https://doi.org/10.14814/phy2.15368

APA

Henriksen, N. L., Hansen, S. H., Lycas, M. D., Pan, X., Eriksen, T., Johansen, L. S., Sprenger, R. R., Ejsing, C. S., Burrin, D. G., Skovgaard, K., Christensen, V. B., Thymann, T., & Pankratova, S. (2022). Cholestasis alters brain lipid and bile acid composition and compromises motor function in neonatal piglets. Physiological Reports, 10(13), [e15368]. https://doi.org/10.14814/phy2.15368

Vancouver

Henriksen NL, Hansen SH, Lycas MD, Pan X, Eriksen T, Johansen LS et al. Cholestasis alters brain lipid and bile acid composition and compromises motor function in neonatal piglets. Physiological Reports. 2022;10(13). e15368. https://doi.org/10.14814/phy2.15368

Author

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. / Cholestasis alters brain lipid and bile acid composition and compromises motor function in neonatal piglets. In: Physiological Reports. 2022 ; Vol. 10, No. 13.

Bibtex

@article{cb2985e270444a0f857346f7a702ea31,

title = "Cholestasis alters brain lipid and bile acid composition and compromises motor function in neonatal piglets",

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.",

keywords = "bile acids, brain, cholestasis, lipids, motor skills",

author = "Henriksen, {Nicole Lind} and Hansen, {Svend H{\o}ime} and Lycas, {Matthew Domenic} and Xiaoyu Pan and Thomas Eriksen and Johansen, {Lars S{\o}ndergaard} and Sprenger, {Richard R.} and Ejsing, {Christer Stenby} and Burrin, {Douglas G.} and Kerstin Skovgaard and Christensen, {Vibeke Brix} and Thomas Thymann and Stanislava Pankratova",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.",

year = "2022",

doi = "10.14814/phy2.15368",

language = "English",

volume = "10",

journal = "Physiological Reports",

issn = "2051-817X",

publisher = "Wiley Periodicals, Inc.",

number = "13",

}

RIS

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

PY - 2022

Y1 - 2022

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.

KW - bile acids

KW - brain

KW - cholestasis

KW - lipids

KW - motor skills

U2 - 10.14814/phy2.15368

DO - 10.14814/phy2.15368

M3 - Journal article

C2 - 35822260

AN - SCOPUS:85133997396

VL - 10

JO - Physiological Reports

JF - Physiological Reports

SN - 2051-817X

IS - 13

M1 - e15368

ER -

ID: 314450092