Effect of methotrexate on cerebellar development in infant
rats |
| |
Authors: | Akihiko SUGIYAMA Jing SUN Kota UEDA Satoshi FURUKAWA Takashi TAKEUCHI |
| |
Institution: | 1) Laboratory of Veterinary Laboratory Medicine, School of Veterinary Medicine, Faculty of Agriculture, Tottori University, Minami 4–101 Koyama-cho, Tottori, Tottori 680–8553, Japan;2) Toxicology and Environmental Science Department, Biological Research Laboratories, Nissan Chemical Industries, Ltd., 1470 Shiraoka, Minamisaitama, Saitama 349–0294, Japan |
| |
Abstract: | 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. |
| |
Keywords: | apoptosis cerebellar hypoplasia external granular layer inhibition of cell proliferation methotrexate rat |
|
|