Effect of Dexamethasone in the Development of O1 or O4 Immunoreactive Oligodendrocyte of the Neonatal Rat

Kim, Myeung Ju; Choi, In Young; Park, Ki Sup; Maskey, Dhiraj; Chang, Young Pyo; Yoo, Young Bok

Abstract

White matter disease (WMD) study, which underlies the subsequent progress of cerebral palsy as well as cognitive impairment of premature and/or low birth weight infants, has been focused either on the hypoxia-ischemia damage or cytokine-induced brain damage related with maternal or fetal inflammation. Also, dexamethasone (DEXA) may increase the risk of neuropsychological problem including adverse cognitive and behavioral outcome in preterm infants. Thus, we hypothesized that perinatal DEXA would damage and trigger the death of developing oligodendrocytes (OL) progenitors, and subsequently disturb myelination. In this study, DEXA was administered to neonatal rats for 3 consecutive days subcutaneously between postnatal day 1 (P1) and P3. By using immunofluorescent staining of stage specific OL progenitor markers such as O4 and O1, the morphological changes of OL progenitors were examined and the apoptosis of OL progenitors were visualized by TUNEL staining. Results depicted that relative number of O1 immunoreactive (IR) cells were less to that of O4 IR cells. Multipolar O1 IR cells with short dendritic processes were observed in both control and DEXA group at P3. In the total O1 immunoreactive cells, the relative percentages of apoptosis cells were calculated at P3 as 8.7% in control, 23.0% in DEXA group. The relative percentages of apoptosis in the total O4 immunoreactive cells were measured at P3 as 3.0% in control and 13.5% in DEXA group. OL progenitors' apoptosis may contribute to the overall reduction of immature OLs in cerebral white matter. Therefore, specific stages of OL maturation could clinically be an important factor in determining the susceptibility to DEXA. To elucidate the disease mechanism of the white matter disease, further investigation may be needed whether OL progenitors' decrease by the DEXA administration affects to the myelin formation as developmental stages.