OXIDATIVE AND MITOCHONDRIAL ALTERATIONS IN ASTROCYTE CULTURES FROM FETAL RATS PRENATALLY EXPOSED TO VALPROIC ACID

The aim of this study was to evaluate astrocyte-enriched cultures derived from fetal brains of valproic acid–treated rats, focusing on mitochondrial respiration, oxidative stress status, and astrocytic marker expression as indicators of metabolic adaptation to prenatal exposure.
Pregnant Sprague–Dawley rats were prenatally exposed to valproic acid (500 mg/kg) or saline at E12.5. Prefrontal cortex cells were isolated at E18 and cultured in vitro. On day 7, cells were fixed or lysed. GFAP expression was assessed by Western blot and immunofluorescence. Oxidative stress SOD/CAT, malonyl dialdehyde (MDA), advanced oxidation protein products (AOPP) and mitochondrial respiration (Seahorse XFe96 analyzer Mito Stress Test) were measured. Statistical analysis used Student’s t-test.
Prenatal exposure to valproic acid significantly altered astrocytic and metabolic parameters in cultured fetal brain cells. GFAP expression was non-significantly decrease in the valproic acid group compared with controls (298±43, 479±161, p<0.13). Oxidative stress analysis revealed reduced SOD activity (0.33±0.06, 0.12±0.04, p<0.006), without significant changes in CAT activity (0.31±0.19, 0.29±0.14, p<0.7), MDA (3.4±0.67, 2.6±0.7), and AOPP (0.39±0.16, 0.2±0.14) levels. Mitochondrial respiration analysis demonstrated smaller drop in OCR after oligomycin in VPA-treated group versus control.
Overall, prenatal valproic acid exposure disrupted astrocytic homeostasis and mitochondrial bioenergetics in fetal brain cultures, evidenced by reduced antioxidant enzyme activities, blunted oligomycin-induced OCR decline, and modest, non-significant changes in GFAP expression.