Erythropoietin Promotes Neural Plasticity and Spatial Memory Recovery in Fimbria-Fornix-Lesioned Rats

Neurorehabil Neural Repair. Nov-Dec 2015;29(10):979-88. doi: 10.1177/1545968315572389. Epub 2015 Apr 6.

Abstract

Background: Erythropoietin (EPO) upregulates the mitogen activated protein kinase (MAPK) cascade, a central signaling pathway in cellular plastic mechanisms, and is critical for normal brain development.

Objective: We hypothesized that EPO could modulate the plasticity mechanisms supporting spatial memory recovery in fimbria-fornix-transected animals.

Methods: Fimbria-fornix was transected in 3 groups of rats. Seven days later, EPO was injected daily for 4 consecutive days within 10 minutes after training on a water maze task.

Results: Our results show that EPO injections 10 minutes after training produced a substantial spatial memory recovery in fimbria-fornix-lesioned animals. In contrast, an EPO injection shortly after fimbria-fornix lesion surgery does not promote spatial-memory recovery. Neither does daily EPO injection 5 hours after the water maze performance. EPO, on the other hand, induced the expression of plasticity-related genes like arc and bdnf, but this effect was independent of training or lesion.

Conclusions: This finding supports our working hypothesis that EPO can modulate transient neuroplastic mechanisms triggered by training in lesioned animals. Consequently, we propose that EPO administration can be a useful trophic factor to promote neural restoration when given in combination with training.

Keywords: BDNF; erythropoietin; fimbria-fornix lesion; neural plasticity.

MeSH terms

  • Analysis of Variance
  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Brain Injuries / complications
  • Brain Injuries / pathology
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Disease Models, Animal
  • Erythropoietin / therapeutic use*
  • Fornix, Brain / injuries*
  • Fornix, Brain / pathology
  • Gene Expression Regulation / drug effects
  • Hemoglobins / metabolism
  • Male
  • Maze Learning / drug effects
  • Memory Disorders / drug therapy*
  • Memory Disorders / etiology
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Neuronal Plasticity / drug effects*
  • Rats
  • Rats, Wistar
  • Recovery of Function / drug effects*
  • Time Factors

Substances

  • Apoptosis Regulatory Proteins
  • Brain-Derived Neurotrophic Factor
  • Hemoglobins
  • Muscle Proteins
  • Nol3 protein, rat
  • Erythropoietin