Erythropoietin improves spatial and nonspatial memory defects by suppressing oxidative damage, inflammation and apoptosis against ethanol neurotoxicity in the developing male rat hippocampus

Abstract

Excessive prenatal exposure to ethanol leads to a condition called fetal alcohol spectrum disorder (FASD). The neurotoxicity of alcohol causes changes in the hippocampus of animals during this time, resulting in impaired hippocampus-related functions, including memory/learning and cognition.The liver and kidneys produce erythropoietin (EPO). The synthesis of EPO by immature neurons also plays a decisive role in the embryonic stage. Also, exogenous EPO exerts its neurocognitive effects in the developing brain under pathophysiological conditions. The aim of this study was to investigate the protective effects of EPO administration after ethanol-induced increased neurodevelopmental toxicity. Male Wistar rat pups were intubated with a dose of 5/27 g/kg/day ethanol from postnatal day 2–10, similar to the last trimester of gestation in humans. Immediately thereafter, EPO (1000 /2000 U/kg, s.c.) were injected. Spatial memory was tested with the Morris water maze (days 36–40) and non-spatial recognition memory with the novel object task (days 39–40). Concentrations of antioxidant enzymes and TNF-α (ELISA) and caspase-3 (immunohistochemical staining) was then performed. The current study shows that EPO administration significantly attenuates spatial and nonspatial memory impairment (P < 0.001). EPO dramatically decreased the amount of caspase 3 positive cells in the CA1 area of the hippocampus (P < 0.01). EPO increased total superoxide dismutase activity (P < 0.05), glutathione concentrations (P < 0.05) and catalase levels (P < 0.001). EPO also attenuated the production of TNF-α and malondialdehyde (P < 0.05). Given EPO's protective effect against ethanol-induced increased neurotoxicity, it is a viable treatment option for FASD, although more research is needed.