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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MDPI AG
2020-07-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/10/8/475 |
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| author | Daniel Chizhikov Randal K. Buddington Igor Y. Iskusnykh |
| author_facet | Daniel Chizhikov Randal K. Buddington Igor Y. Iskusnykh |
| author_sort | Daniel Chizhikov |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T18:14:45Z |
| format | Article |
| id | doaj.art-3398467aab1a487a9714d6aa4d360aad |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-10T18:14:45Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-3398467aab1a487a9714d6aa4d360aad2023-11-20T07:45:32ZengMDPI AGBrain Sciences2076-34252020-07-0110847510.3390/brainsci10080475Effects of Phosphatidylserine Source of Docosahexaenoic Acid on Cerebellar Development in Preterm PigsDaniel Chizhikov0Randal K. Buddington1Igor Y. Iskusnykh2School of Health Studies, University of Memphis, Memphis, TN 38152, USASchool of Health Studies, University of Memphis, Memphis, TN 38152, USADepartment of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USAPreterm 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.https://www.mdpi.com/2076-3425/10/8/475preterm infantsbrain developmentphosphatidylserinedocosahexaenoic acid (DHA)cerebellumpig |
| spellingShingle | Daniel Chizhikov Randal K. Buddington Igor Y. Iskusnykh Effects of Phosphatidylserine Source of Docosahexaenoic Acid on Cerebellar Development in Preterm Pigs Brain Sciences preterm infants brain development phosphatidylserine docosahexaenoic acid (DHA) cerebellum pig |
| 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 | preterm infants brain development phosphatidylserine docosahexaenoic acid (DHA) cerebellum pig |
| url | https://www.mdpi.com/2076-3425/10/8/475 |
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