Erythropoietin shows gender dependent positive effects on social deficits, learning/memory impairments, neuronal loss and neuroinflammation in the lipopolysaccharide induced rat model of autism

Neuropeptides. 2020 Oct;83:102073. doi: 10.1016/j.npep.2020.102073. Epub 2020 Jul 17.

Abstract

We aimed to evaluate the effects of EPO in the lipopolysaccharide (LPS) induced rat model of autism in terms of social deficits, learning and memory impairments, as well as their neurochemical correlates. Sixteen female Sprague Dawley rats randomly distributed into two equel groups, then were caged with fertile males for mating. At the 10th day of pregnancy, 0.5 ml %0,9 NaCl saline was given to first group, 100 μg/kg LPS was given to second group to induce autism. On postnatal 21th day, forty-eight littermates were divided into four groups as; 8 male, 8 female controls, 16 male and 16 female LPS-exposed. Then, LPS groups were also divided in to two groups as saline (1 mg/kg/day) and EPO 600 U/kg/day groups, and animals were treated 45 days. At 50th day, after behavioral evaluations, brain levels of TNF-α, nerve growth factor (NGF) were measured. Histologically, hippocampal neuronal density and GFAP expression were assessed. Three-chamber sociability and social novelty test, passive avoidance learning test were revealed significant differences among the EPO and control groups. Histologically, hippocampal CA1 & CA3 regions displayed significant alterations regarding gliosis (GFAP-positive cells) and regarding frontal cortical thickness in EPO groups compare to controls. Biochemical measurements of the brain levels of TNF-α and NGF levels showed significant differences between controls and EPO groups. According to our findings EPO treatment has beneficial effects on ASD-like symptoms, learning and memory processes, neuronal loss and neuroinflammation in the LPS induced rat model of autism, with some gender differences through inflammatory and neurotrophic pathways.

Keywords: Autism spectrum disorders; Erythropoietin; NGF; Neuroinflammation; TNF-α.

MeSH terms

  • Animals
  • Autistic Disorder / chemically induced
  • Autistic Disorder / drug therapy*
  • Autistic Disorder / metabolism
  • Autistic Disorder / pathology
  • Avoidance Learning / drug effects
  • Behavior, Animal / drug effects*
  • Disease Models, Animal
  • Erythropoietin / pharmacology*
  • Female
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Lipopolysaccharides
  • Male
  • Memory / drug effects
  • Memory Disorders / drug therapy*
  • Memory Disorders / metabolism
  • Memory Disorders / pathology
  • Neurons / drug effects*
  • Neurons / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Social Behavior
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Erythropoietin