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.

Perinatal Exposure to Glufosinate Ammonium Herbicide Impairs Neurogenesis and Neuroblast Migration through Cytoskeleton Destabilization

“…These data suggested that the SVZ, lining the walls of the lateral ventricles, is sensitive to exogenous toxicants, and subsequently may constitute the real “window of the brain” as proposed by many authors (Gross and Weindl, 1987 ; Moyse et al, 2006 ; Joly et al, 2007 ; Lin et al, 2015 ). Such an assumption is reinforced by a recent study showing that perinatal exposure to another environmental toxicant, methotrexate, also led to SVZ alterations (Hirako et al, 2016 ). These aversive effects of exogenous compounds on the SVZ could be inherent to its intrinsic structure characterized by permeable fenestrated capillaries and thus a lack of endothelial blood–brain-barrier (BBB) (Johnson and Gross, 1993 ; Tavazoie et al, 2008 ).…”

“…In line with this, Autism Spectrum Disorders (ASD) are thought to be associated with alterations in neonatal neurogenesis in the SVZ (Kotagiri et al, 2014 ). Indeed, it was shown that neurobehavioral defects concomitant to cellular SVZ abnormalities were induced by perinatal exposure to methotrexate (Seigers et al, 2015 ; Hirako et al, 2016 ).…”