title: Effect of methotrexate on rostral migratory stream in newborn rats.
abstract: Two-day-old rats were treated with subcutaneous injections of methotrexate (MTX) 5 mg/kg and 150 mg/kg, and their rostral migratory streams (RMS) were examined time-dependently. MTX treatment increased pyknotic and TUNEL-positive cells and decreased mitotic and phospho-Histone H3-positive cells at almost all time points in the vertical arm, elbow and horizontal arm regions of the RMS. There were more TUNEL-positive cells ratio in the MTX 150 mg/kg group than in the MTX 5 mg/kg group. Treatment with MTX 150 mg/kg decreased the cellularity in the vertical arm region on Postnatal day (PD) 4, but that with the MTX 5 mg/kg did not. TUNEL-positive cells ratio was the highest in the vertical arm region, followed by elbow and horizontal regions in both MTX-treated groups. TUNEL-positive cells ratio in the vertical arm and elbow regions reached their peaks on PD 4 in both MTX-treated groups, and both MTX-treatments significantly decreased Phospho-Histone H3-positive cells ratio on PDs 2.5 and 3 in the vertical arm, elbow and horizontal arm regions. The phospho-Histone H3-positive cells ratio in the vertical arm region recovered on PD4 in the MTX 150 mg/kg group. These findings suggested that RMS required a great amount of folic acid on PD 2 and that the folic acid-requirement differed depending on the anatomical region of the RMS. To our knowledge, this is the first report demonstrating the effect of MTX on the RMS and the necessity of the folic acid metabolism on RMS development in newborn rats.
authors.affiliation: Department of Veterinary Laboratory Medicine, School of Veterinary Medicine, Faculty of Agriculture, Tottori University, Minami 4-101 Koyama-cho, Tottori, Tottori 680-8553, Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Hirako
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.forename: Satoshi
authors.initials: S
authors.lastname: Furukawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005493:Folic Acid Antagonists / Q000009:adverse effects*; D020547:Lateral Ventricles / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D051381:Rats
chemical_list: D005493:Folic Acid Antagonists; D008727:Methotrexate