Effect of methotrexate on cerebellar development in infantrats

Journal of Veterinary Medical Science

Jing SUN²  Satoshi FURUKAWA¹  Takashi TAKEUCHI²  Kota UEDA²  Akihiko SUGIYAMA² 

[1] Toxicology and Environmental Science Department, Biological Research Laboratories, Nissan Chemical Industries, Ltd., 1470 Shiraoka, Minamisaitama, Saitama 349�?0294, Japan;Laboratory of Veterinary Laboratory Medicine, School of Veterinary Medicine, Faculty of Agriculture, Tottori University, Minami 4�?101 Koyama-cho, Tottori, Tottori 680�?8553, Japan

关键词: apoptosis;    cerebellar hypoplasia;    external granular layer;    inhibition of cell proliferation;    methotrexate;    rat;   

DOI  :  10.1292/jvms.14-0475

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(51)Cited-By(2)Six-day-old rats were treated intraperitoneal injections with methotrexate 1mg/kg, and the cerebellum was examined. Both the length and width of the vermis decreasedin 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 detectedon 2 and 3 DAT in the methotrexate group. By 4 DAT, the width of the external granularlayer of the methotrexate group was indistinguishable from the control, and by 8 DAT, itwas greater than that of the control. The molecular layer of methotrexate group on 8 and15 DAT was thinner than that of the control. On 1 DAT, in the methotrexate group, therewere many TUNEL and cleaved caspase-3-positive granular cells throughout the externalgranular 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 thecontrol and tended to increase on 2�?4 DAT. The p21-positive-rate of the external granulecells in the MTX group was higher than in the control on 1�?4 DAT. These results suggestedthat methotrexate exposure on postnatal day 6 induces a delay, slowing in the migration ofexternal granular cells to the inner granular layer, attributed to decrease or inhibitionin the production of external granular cells that had arisen from apoptosis and thedecrease in cell proliferative activity, resulting in cerebellar hypoplasia.

【 授权许可】

Unknown