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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...

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Autores principales: SUGIYAMA, Akihiko, SUN, Jing, UEDA, Kota, FURUKAWA, Satoshi, TAKEUCHI, Takashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Japanese Society of Veterinary Science 2015
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.
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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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