Continuous intraventricular infusion of erythropoietin exerts neuroprotective/rescue effects upon Parkinson's disease model of rats with enhanced neurogenesis

Tomohito Kadota, Tetsuro Shingo, Takao Yasuhara, Naoki Tajiri, Akihiko Kondo, Takamasa Morimoto, Wen Ji Yuan, Feifei Wang, Tanefumi Baba, Koji Tokunaga, Yasuyuki Miyoshi, Isao Date

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Parkinson's disease (PD) is characterized by degeneration of nigrostriatal dopaminergic neuronal systems. Several therapeutic tools for PD include medication using l-DOPA and surgeries such as deep brain stimulation are established. However, the therapies are considered as symptomatic therapy, but not basic remedy for PD and a new regenerative therapy would be desired to explore. In this study, the neuroprotective/rescue effects of erythropoietin (EPO), a well known hematopoietic hormone, on dopaminergic neurons were explored with neurogeneic potencies of EPO. EPO (100 IU/day) was continuously administered with micro-osmotic pump for a week to PD model of rats induced by intrastriatal 6-hydroxydopamine (6-OHDA) injection with subsequent behavioral and immunohistochemical investigations. The number of amphetamine-induced rotations of EPO-treated rats significantly decreased, compared to the control rats. The preservation of dopaminergic neurons of EPO-treated rats were confirmed by tyrosine hydroxylase staining and Fluoro-Gold staining. The number of bromodeoxyuridine (BrdU)/polysialic acid-neural cell adhesion molecule (PSA-NCAM) double positive cells in the subventricular zone of EPO-treated rats significantly increased with migratory potencies to the damaged striatum, compared to the control rats. Furthermore, TUNEL staining and phosphorylated Akt staining revealed that the neuroprotective/rescue effects of EPO might be mediated by anti-apoptotic effects through the increase of phosphorylated Akt. These results suggest that continuous low dose infusion of EPO exerts neuroprotective/rescue effects with neurogeneic potentials. EPO might be a strong tool for PD therapy, although the further experiments should be added.

Original languageEnglish
Pages (from-to)120-127
Number of pages8
JournalBrain Research
Volume1254
DOIs
Publication statusPublished - Feb 13 2009

Keywords

  • 6-OHDA
  • Apoptosis
  • Dopaminergic neuron
  • Neurogenesis
  • Subventricular zone

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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