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Effects of Phosphatidylserine Source of Docosahexaenoic Acid on Cerebellar Development in Preterm Pigs

Preterm birth, a major contributor to infant mortality and morbidity, impairs development of the cerebellum, the brain region involved in cognitive processing and motor function. Previously, we showed that at term-equivalent age, preterm pigs that received formula supplemented with docosahexaenoic a...

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Autores principales: Chizhikov, Daniel, Buddington, Randal K., Iskusnykh, Igor Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464467/
https://www.ncbi.nlm.nih.gov/pubmed/32718081
http://dx.doi.org/10.3390/brainsci10080475
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author Chizhikov, Daniel
Buddington, Randal K.
Iskusnykh, Igor Y.
author_facet Chizhikov, Daniel
Buddington, Randal K.
Iskusnykh, Igor Y.
author_sort Chizhikov, Daniel
collection PubMed
description Preterm birth, a major contributor to infant mortality and morbidity, impairs development of the cerebellum, the brain region involved in cognitive processing and motor function. Previously, we showed that at term-equivalent age, preterm pigs that received formula supplemented with docosahexaenoic acid (DHA) esterified to phosphatidylserine (PS) had cerebellar weights similar to those of newborn term pigs and were heavier than control preterm pigs. However, whether PS-DHA promotes the development of specific cerebellar cell populations or enhances key developmental processes remains unknown. Here we investigated the effects of the PS-DHA on development of the cerebellum in preterm pigs delivered via caesarean section and reared for ten days on a milk replacer with either PS-DHA (experimental group) or sunflower oil (control group). Upon necropsy, key cerebellar populations were analyzed using immunohistochemistry. Consumption of PS-DHA was associated with the expansion of undifferentiated granule cell precursors and increased proliferation in the external granule cell layer (EGL). Preterm pigs that received PS-DHA also had significantly fewer apoptotic cells in the internal granule cell layer (IGL) that contains differentiated granule neurons. PS-DHA did not affect the number of differentiating granule cells in the inner EGL, thickness of the inner EGL, density of Purkinje cells, or Bergmann glial fibers, or diameter of Purkinje cells. Thus, PS-DHA may support cerebellar development in preterm subjects by enhancing proliferation of granule cells, a process specifically inhibited by preterm birth, and increasing the survival of granule cells in the IGL. These findings suggest that PS-DHA is a promising candidate for clinical studies directed at enhancing brain development.
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spelling pubmed-74644672020-09-04 Effects of Phosphatidylserine Source of Docosahexaenoic Acid on Cerebellar Development in Preterm Pigs Chizhikov, Daniel Buddington, Randal K. Iskusnykh, Igor Y. Brain Sci Article Preterm birth, a major contributor to infant mortality and morbidity, impairs development of the cerebellum, the brain region involved in cognitive processing and motor function. Previously, we showed that at term-equivalent age, preterm pigs that received formula supplemented with docosahexaenoic acid (DHA) esterified to phosphatidylserine (PS) had cerebellar weights similar to those of newborn term pigs and were heavier than control preterm pigs. However, whether PS-DHA promotes the development of specific cerebellar cell populations or enhances key developmental processes remains unknown. Here we investigated the effects of the PS-DHA on development of the cerebellum in preterm pigs delivered via caesarean section and reared for ten days on a milk replacer with either PS-DHA (experimental group) or sunflower oil (control group). Upon necropsy, key cerebellar populations were analyzed using immunohistochemistry. Consumption of PS-DHA was associated with the expansion of undifferentiated granule cell precursors and increased proliferation in the external granule cell layer (EGL). Preterm pigs that received PS-DHA also had significantly fewer apoptotic cells in the internal granule cell layer (IGL) that contains differentiated granule neurons. PS-DHA did not affect the number of differentiating granule cells in the inner EGL, thickness of the inner EGL, density of Purkinje cells, or Bergmann glial fibers, or diameter of Purkinje cells. Thus, PS-DHA may support cerebellar development in preterm subjects by enhancing proliferation of granule cells, a process specifically inhibited by preterm birth, and increasing the survival of granule cells in the IGL. These findings suggest that PS-DHA is a promising candidate for clinical studies directed at enhancing brain development. MDPI 2020-07-23 /pmc/articles/PMC7464467/ /pubmed/32718081 http://dx.doi.org/10.3390/brainsci10080475 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chizhikov, Daniel
Buddington, Randal K.
Iskusnykh, Igor Y.
Effects of Phosphatidylserine Source of Docosahexaenoic Acid on Cerebellar Development in Preterm Pigs
title Effects of Phosphatidylserine Source of Docosahexaenoic Acid on Cerebellar Development in Preterm Pigs
title_full Effects of Phosphatidylserine Source of Docosahexaenoic Acid on Cerebellar Development in Preterm Pigs
title_fullStr Effects of Phosphatidylserine Source of Docosahexaenoic Acid on Cerebellar Development in Preterm Pigs
title_full_unstemmed Effects of Phosphatidylserine Source of Docosahexaenoic Acid on Cerebellar Development in Preterm Pigs
title_short Effects of Phosphatidylserine Source of Docosahexaenoic Acid on Cerebellar Development in Preterm Pigs
title_sort effects of phosphatidylserine source of docosahexaenoic acid on cerebellar development in preterm pigs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464467/
https://www.ncbi.nlm.nih.gov/pubmed/32718081
http://dx.doi.org/10.3390/brainsci10080475
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