Erythropoietin Attenuates Anxiety and Neurodevelopmental Neurotoxicity in Male Rats with Fetal Alcohol Spectrum Disorder via Increased BDNF-Positive Cells, Astrogliosis Suppression, and Reduced Hippocampal Cell Death.

Objective: The term "fetal alcohol spectrum disorder" (FASD) refers to a variety of negative consequences that may develop in children born to women who have consumed alcohol during pregnancy. Anxiety disorders are common in FASD. Animals exposed to alcohol exhibit anxiety-like traits. Erythropoietin (EPO) is produced by the kidneys and liver. The synthesis of EPO by immature neurons also plays a crucial role in the embryonic stage. In addition, EPO inhibits astrogliosis and cell death while increasing the number of brain-derived neurotrophic factor (BDNF)-positive cells, which is linked to reductions in anxiety-like behavior and neuronal damage. This study investigated the protective effects of EPO on ethanol-induced neurotoxicity in the hippocampus of rat pups.

Method: The intubation of the total daily dose of ethanol (5/27 g/kg/day) was started from PD 2 to PD 10 (corresponding to the third trimester of pregnancy in humans). After intubation, 1000 and 2000 U/kg EPO were injected subcutaneously. The elevated plus maze (EPM) was performed 39 days after the birth of the pups to determine the levels of anxiety. Immunohistochemical staining was then performed to determine GFAP and BDNF levels 40 days after birth. Nissl staining was done to measure necrotic cell death.

Results: EPO administration significantly improved the anxious behavior associated with FASD (P< 0.001). EPO significantly increased BDNF levels (P< 0.001), decreased GFAP expression (P< 0.001), and attenuated alcohol neurotoxicity-induced necrotic cell death (P< 0.001).

Conclusions: EPO treatment providing protection against ethanol neurotoxicity, which consequently leads to lower anxiety levels.