Maternal dietary folate imbalance alters cerebellar astrocyte morphology and density in offspring

Background: Maternal folate usage is essential for neurodevelopment, but its effects on cerebellar structure are unclear. Cerebellum undergoes a protracted period of development, making it sensitive to maternal nutritional imbalances. Astrocytes are necessary for cerebellar cortex structure and func...

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Main Authors: Philip Maseghe Mwachaka, Peter Gichangi, Adel Abdelmalek, Paul Odula, Julius Ogeng’o
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:IBRO Neuroscience Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667242124001167
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author Philip Maseghe Mwachaka
Peter Gichangi
Adel Abdelmalek
Paul Odula
Julius Ogeng’o
author_facet Philip Maseghe Mwachaka
Peter Gichangi
Adel Abdelmalek
Paul Odula
Julius Ogeng’o
author_sort Philip Maseghe Mwachaka
collection DOAJ
description Background: Maternal folate usage is essential for neurodevelopment, but its effects on cerebellar structure are unclear. Cerebellum undergoes a protracted period of development, making it sensitive to maternal nutritional imbalances. Astrocytes are necessary for cerebellar cortex structure and function. This study examined the impact of varying maternal dietary folate levels on the morphology and density of cerebellar astrocytes in rat offspring. Materials and methods: Twelve adult female rats (Rattus norvegicus) were randomly allocated to one of four premixed food groups: standard (2 mg/kg), folate-deficient (0 mg/kg), folate-supplemented (8 mg/kg), or folate supra-supplemented (40 mg/kg). The rats began their diets 14 days before mating and continued throughout pregnancy and lactation. On postnatal day 35, five pups from each group were sacrificed and their cerebellums were processed for immunohistochemical examination. The cerebellar astrocytes were labelled with an antibody against Glial Fibrillary Acid Protein (GFAP). Results: The offspring of the folate-deficient diet group exhibited few Bergmann and granule layer astrocytes. The Bergmann radial glial processes in this group were thinner, discontinuous, poorly organised, and had unclear end feet compared to controls. Conversely, the folate-supplemented group showed a predominance of well-organized Bergmann glia astrocytes with distinct, thicker, and densely packed processes, ending in clear conical pial foot processes. In the supra-supplemented group, there was evidence of astrogliosis in the form of large granule layer astrocytes with extended cytoplasmic projections. The Bergmann glia in this group were fewer and more varied in distribution and morphology. Some locations had many astrocytic processes, whereas others had none. Some processes were discontinuous and tortuous. The proportion of cerebellar cortical GFAP immunoreactive cells in folate-deficient diet, controls, folate-supplemented, and folate supra-supplemented groups were 2.09 ± 0.06 %, 4.69 ± 0.12 %, 10.14 ± 0.67 %, and 23.12 ± 3.48 %, respectively (p < 0.001). Conclusions: These findings imply that both folate deficiency and excess supplementation in pregnancy can impair normal cerebellar astrocyte development, highlighting the importance of balanced folate levels during pregnancy for optimal neurodevelopmental outcomes.
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spelling doaj-art-7109c1eeab504e52b9288efdbb994bbd2025-08-20T02:39:37ZengElsevierIBRO Neuroscience Reports2667-24212025-06-0118788710.1016/j.ibneur.2024.12.009Maternal dietary folate imbalance alters cerebellar astrocyte morphology and density in offspringPhilip Maseghe Mwachaka0Peter Gichangi1Adel Abdelmalek2Paul Odula3Julius Ogeng’o4Corresponding author.; Department of Human Anatomy and Medical Physiology, Faculty of Health Sciences, University of Nairobi, P.O. Box 30197-00100, Nairobi, KenyaDepartment of Human Anatomy and Medical Physiology, Faculty of Health Sciences, University of Nairobi, P.O. Box 30197-00100, Nairobi, KenyaDepartment of Human Anatomy and Medical Physiology, Faculty of Health Sciences, University of Nairobi, P.O. Box 30197-00100, Nairobi, KenyaDepartment of Human Anatomy and Medical Physiology, Faculty of Health Sciences, University of Nairobi, P.O. Box 30197-00100, Nairobi, KenyaDepartment of Human Anatomy and Medical Physiology, Faculty of Health Sciences, University of Nairobi, P.O. Box 30197-00100, Nairobi, KenyaBackground: Maternal folate usage is essential for neurodevelopment, but its effects on cerebellar structure are unclear. Cerebellum undergoes a protracted period of development, making it sensitive to maternal nutritional imbalances. Astrocytes are necessary for cerebellar cortex structure and function. This study examined the impact of varying maternal dietary folate levels on the morphology and density of cerebellar astrocytes in rat offspring. Materials and methods: Twelve adult female rats (Rattus norvegicus) were randomly allocated to one of four premixed food groups: standard (2 mg/kg), folate-deficient (0 mg/kg), folate-supplemented (8 mg/kg), or folate supra-supplemented (40 mg/kg). The rats began their diets 14 days before mating and continued throughout pregnancy and lactation. On postnatal day 35, five pups from each group were sacrificed and their cerebellums were processed for immunohistochemical examination. The cerebellar astrocytes were labelled with an antibody against Glial Fibrillary Acid Protein (GFAP). Results: The offspring of the folate-deficient diet group exhibited few Bergmann and granule layer astrocytes. The Bergmann radial glial processes in this group were thinner, discontinuous, poorly organised, and had unclear end feet compared to controls. Conversely, the folate-supplemented group showed a predominance of well-organized Bergmann glia astrocytes with distinct, thicker, and densely packed processes, ending in clear conical pial foot processes. In the supra-supplemented group, there was evidence of astrogliosis in the form of large granule layer astrocytes with extended cytoplasmic projections. The Bergmann glia in this group were fewer and more varied in distribution and morphology. Some locations had many astrocytic processes, whereas others had none. Some processes were discontinuous and tortuous. The proportion of cerebellar cortical GFAP immunoreactive cells in folate-deficient diet, controls, folate-supplemented, and folate supra-supplemented groups were 2.09 ± 0.06 %, 4.69 ± 0.12 %, 10.14 ± 0.67 %, and 23.12 ± 3.48 %, respectively (p < 0.001). Conclusions: These findings imply that both folate deficiency and excess supplementation in pregnancy can impair normal cerebellar astrocyte development, highlighting the importance of balanced folate levels during pregnancy for optimal neurodevelopmental outcomes.http://www.sciencedirect.com/science/article/pii/S2667242124001167CerebellumMaternal folate useOffspringAstrocytes
spellingShingle Philip Maseghe Mwachaka
Peter Gichangi
Adel Abdelmalek
Paul Odula
Julius Ogeng’o
Maternal dietary folate imbalance alters cerebellar astrocyte morphology and density in offspring
IBRO Neuroscience Reports
Cerebellum
Maternal folate use
Offspring
Astrocytes
title Maternal dietary folate imbalance alters cerebellar astrocyte morphology and density in offspring
title_full Maternal dietary folate imbalance alters cerebellar astrocyte morphology and density in offspring
title_fullStr Maternal dietary folate imbalance alters cerebellar astrocyte morphology and density in offspring
title_full_unstemmed Maternal dietary folate imbalance alters cerebellar astrocyte morphology and density in offspring
title_short Maternal dietary folate imbalance alters cerebellar astrocyte morphology and density in offspring
title_sort maternal dietary folate imbalance alters cerebellar astrocyte morphology and density in offspring
topic Cerebellum
Maternal folate use
Offspring
Astrocytes
url http://www.sciencedirect.com/science/article/pii/S2667242124001167
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