Tracking of Internal Granular Progenitors Responding to Valproic Acid in the Cerebellar Cortex of Infant Ferrets

Internal granular progenitors (IGPs) in the developing cerebellar cortex of ferrets differentiate towards neural and glial lineages. The present study tracked IGPs that proliferated in response to valproic acid (VPA) to determine their fate during cerebellar cortical histogenesis. Ferret kits were u...

Full description

Bibliographic Details
Main Authors: Shiori Kamiya, Tetsuya Kobayashi, Kazuhiko Sawada
Format: Article
Language:English
Published: MDPI AG 2024-02-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/13/4/308
_version_ 1827343959035215872
author Shiori Kamiya
Tetsuya Kobayashi
Kazuhiko Sawada
author_facet Shiori Kamiya
Tetsuya Kobayashi
Kazuhiko Sawada
author_sort Shiori Kamiya
collection DOAJ
description Internal granular progenitors (IGPs) in the developing cerebellar cortex of ferrets differentiate towards neural and glial lineages. The present study tracked IGPs that proliferated in response to valproic acid (VPA) to determine their fate during cerebellar cortical histogenesis. Ferret kits were used to administer VPA (200 μg/g body weight) on postnatal days 6 and 7. EdU and BrdU were injected on postnatal days 5 and 7, respectively, to label the post-proliferative and proliferating cells when exposed to VPA. At postnatal day 20, when the external granule layer was most expanded, EdU- and BrdU-single-labeled cells were significantly denser in the inner granular layer of VPA-exposed ferrets than in controls. No EdU- or BrdU-labeling was found in Purkinje cells and molecular layer interneurons. Significantly higher percentages of NeuN and Pax6 immunostaining in VPA-exposed ferrets revealed VPA-induced differentiation of IGPs towards granular neurons in BrdU-single-labeled cells. In contrast, both EdU- and BrdU-single-labeled cells exhibited significantly greater percentages of PCNA immunostaining, which appeared in immature Bergman glia, in the internal granular layer of VPA-exposed ferrets. These findings suggest that VPA affects the proliferation of IGPs to induce differentiative division towards granular neurons as well as post-proliferative IGPs toward differentiation into Bergmann glia.
first_indexed 2024-03-07T22:38:01Z
format Article
id doaj.art-cabe0dea61164984b0eae1a7af72bcd8
institution Directory Open Access Journal
issn 2073-4409
language English
last_indexed 2024-03-07T22:38:01Z
publishDate 2024-02-01
publisher MDPI AG
record_format Article
series Cells
spelling doaj.art-cabe0dea61164984b0eae1a7af72bcd82024-02-23T15:11:40ZengMDPI AGCells2073-44092024-02-0113430810.3390/cells13040308Tracking of Internal Granular Progenitors Responding to Valproic Acid in the Cerebellar Cortex of Infant FerretsShiori Kamiya0Tetsuya Kobayashi1Kazuhiko Sawada2Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, JapanDivision of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, JapanDepartment of Nutrition, Faculty of Medical and Health Sciences, Tsukuba International University, Tsuchiura 300-0051, JapanInternal granular progenitors (IGPs) in the developing cerebellar cortex of ferrets differentiate towards neural and glial lineages. The present study tracked IGPs that proliferated in response to valproic acid (VPA) to determine their fate during cerebellar cortical histogenesis. Ferret kits were used to administer VPA (200 μg/g body weight) on postnatal days 6 and 7. EdU and BrdU were injected on postnatal days 5 and 7, respectively, to label the post-proliferative and proliferating cells when exposed to VPA. At postnatal day 20, when the external granule layer was most expanded, EdU- and BrdU-single-labeled cells were significantly denser in the inner granular layer of VPA-exposed ferrets than in controls. No EdU- or BrdU-labeling was found in Purkinje cells and molecular layer interneurons. Significantly higher percentages of NeuN and Pax6 immunostaining in VPA-exposed ferrets revealed VPA-induced differentiation of IGPs towards granular neurons in BrdU-single-labeled cells. In contrast, both EdU- and BrdU-single-labeled cells exhibited significantly greater percentages of PCNA immunostaining, which appeared in immature Bergman glia, in the internal granular layer of VPA-exposed ferrets. These findings suggest that VPA affects the proliferation of IGPs to induce differentiative division towards granular neurons as well as post-proliferative IGPs toward differentiation into Bergmann glia.https://www.mdpi.com/2073-4409/13/4/308cerebellumVPAneurogenesisBergmann gliaferret
spellingShingle Shiori Kamiya
Tetsuya Kobayashi
Kazuhiko Sawada
Tracking of Internal Granular Progenitors Responding to Valproic Acid in the Cerebellar Cortex of Infant Ferrets
Cells
cerebellum
VPA
neurogenesis
Bergmann glia
ferret
title Tracking of Internal Granular Progenitors Responding to Valproic Acid in the Cerebellar Cortex of Infant Ferrets
title_full Tracking of Internal Granular Progenitors Responding to Valproic Acid in the Cerebellar Cortex of Infant Ferrets
title_fullStr Tracking of Internal Granular Progenitors Responding to Valproic Acid in the Cerebellar Cortex of Infant Ferrets
title_full_unstemmed Tracking of Internal Granular Progenitors Responding to Valproic Acid in the Cerebellar Cortex of Infant Ferrets
title_short Tracking of Internal Granular Progenitors Responding to Valproic Acid in the Cerebellar Cortex of Infant Ferrets
title_sort tracking of internal granular progenitors responding to valproic acid in the cerebellar cortex of infant ferrets
topic cerebellum
VPA
neurogenesis
Bergmann glia
ferret
url https://www.mdpi.com/2073-4409/13/4/308
work_keys_str_mv AT shiorikamiya trackingofinternalgranularprogenitorsrespondingtovalproicacidinthecerebellarcortexofinfantferrets
AT tetsuyakobayashi trackingofinternalgranularprogenitorsrespondingtovalproicacidinthecerebellarcortexofinfantferrets
AT kazuhikosawada trackingofinternalgranularprogenitorsrespondingtovalproicacidinthecerebellarcortexofinfantferrets