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Effect of methotrexate on cerebellar development in infant rats
Six-day-old rats were treated intraperitoneal injections with methotrexate 1 mg/kg, and the cerebellum was examined. Both the length and width of the vermis decreased in the methotrexate-treated group instead of the control from 4 day after treatment (DAT) onward. A significant reduction in the widt...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Japanese Society of Veterinary Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527500/ https://www.ncbi.nlm.nih.gov/pubmed/25754651 http://dx.doi.org/10.1292/jvms.14-0475 |
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author | SUGIYAMA, Akihiko SUN, Jing UEDA, Kota FURUKAWA, Satoshi TAKEUCHI, Takashi |
author_facet | SUGIYAMA, Akihiko SUN, Jing UEDA, Kota FURUKAWA, Satoshi TAKEUCHI, Takashi |
author_sort | SUGIYAMA, Akihiko |
collection | PubMed |
description | Six-day-old rats were treated intraperitoneal injections with methotrexate 1 mg/kg, and the cerebellum was examined. Both the length and width of the vermis decreased in the methotrexate-treated group instead of the control from 4 day after treatment (DAT) onward. A significant reduction in the width of the external granular layer was detected on 2 and 3 DAT in the methotrexate group. By 4 DAT, the width of the external granular layer of the methotrexate group was indistinguishable from the control, and by 8 DAT, it was greater than that of the control. The molecular layer of methotrexate group on 8 and 15 DAT was thinner than that of the control. On 1 DAT, in the methotrexate group, there were many TUNEL and cleaved caspase-3-positive granular cells throughout the external granular layer, and they decreased time-dependently. On 1 DAT, in the methotrexate group, phospho-histone H3-positive cells in the external granular layer were fewer than in the control and tended to increase on 2–4 DAT. The p21-positive-rate of the external granule cells in the MTX group was higher than in the control on 1–4 DAT. These results suggested that methotrexate exposure on postnatal day 6 induces a delay, slowing in the migration of external granular cells to the inner granular layer, attributed to decrease or inhibition in the production of external granular cells that had arisen from apoptosis and the decrease in cell proliferative activity, resulting in cerebellar hypoplasia. |
format | Online Article Text |
id | pubmed-4527500 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Japanese Society of Veterinary Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45275002015-08-07 Effect of methotrexate on cerebellar development in infant rats SUGIYAMA, Akihiko SUN, Jing UEDA, Kota FURUKAWA, Satoshi TAKEUCHI, Takashi J Vet Med Sci Pathology Six-day-old rats were treated intraperitoneal injections with methotrexate 1 mg/kg, and the cerebellum was examined. Both the length and width of the vermis decreased in the methotrexate-treated group instead of the control from 4 day after treatment (DAT) onward. A significant reduction in the width of the external granular layer was detected on 2 and 3 DAT in the methotrexate group. By 4 DAT, the width of the external granular layer of the methotrexate group was indistinguishable from the control, and by 8 DAT, it was greater than that of the control. The molecular layer of methotrexate group on 8 and 15 DAT was thinner than that of the control. On 1 DAT, in the methotrexate group, there were many TUNEL and cleaved caspase-3-positive granular cells throughout the external granular layer, and they decreased time-dependently. On 1 DAT, in the methotrexate group, phospho-histone H3-positive cells in the external granular layer were fewer than in the control and tended to increase on 2–4 DAT. The p21-positive-rate of the external granule cells in the MTX group was higher than in the control on 1–4 DAT. These results suggested that methotrexate exposure on postnatal day 6 induces a delay, slowing in the migration of external granular cells to the inner granular layer, attributed to decrease or inhibition in the production of external granular cells that had arisen from apoptosis and the decrease in cell proliferative activity, resulting in cerebellar hypoplasia. The Japanese Society of Veterinary Science 2015-03-05 2015-07 /pmc/articles/PMC4527500/ /pubmed/25754651 http://dx.doi.org/10.1292/jvms.14-0475 Text en ©2015 The Japanese Society of Veterinary Science http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. |
spellingShingle | Pathology SUGIYAMA, Akihiko SUN, Jing UEDA, Kota FURUKAWA, Satoshi TAKEUCHI, Takashi Effect of methotrexate on cerebellar development in infant rats |
title | Effect of methotrexate on cerebellar development in infant
rats |
title_full | Effect of methotrexate on cerebellar development in infant
rats |
title_fullStr | Effect of methotrexate on cerebellar development in infant
rats |
title_full_unstemmed | Effect of methotrexate on cerebellar development in infant
rats |
title_short | Effect of methotrexate on cerebellar development in infant
rats |
title_sort | effect of methotrexate on cerebellar development in infant
rats |
topic | Pathology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527500/ https://www.ncbi.nlm.nih.gov/pubmed/25754651 http://dx.doi.org/10.1292/jvms.14-0475 |
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