Journal of Molecular Neuroscience

, Volume 50, Issue 3, pp 542–550

Knocking Out DJ-1 Attenuates Astrocytes Neuroprotection Against 6-Hydroxydopamine Toxicity

  • Nirit Lev
  • Yael Barhum
  • Tali Ben-Zur
  • Eldad Melamed
  • Israel Steiner
  • Daniel Offen
Article

DOI: 10.1007/s12031-013-9984-9

Cite this article as:
Lev, N., Barhum, Y., Ben-Zur, T. et al. J Mol Neurosci (2013) 50: 542. doi:10.1007/s12031-013-9984-9

Abstract

Astrocytes are the most abundant glial cell type in the brain. Impairment in astrocyte functions can critically influence neuronal survival and leads to neurodegeneration. Parkinson’s disease (PD) is a common neurodegenerative disorder, characterized by motor dysfunction that results from progressive neuronal loss. Astrocytic dysfunction was demonstrated in human samples and in experimental models of PD. Mutations in DJ-1 (PARK7) leading to loss of functional protein cause familial PD and enhance sensitivity to oxidative insults. Recently, an increase in DJ-1’s expression was found in reactive astrocytes in various neurodegenerative disorders. Here we show that lack of DJ-1 attenuates astrocytes’ ability to support neuronal cells, thereby leading to accelerated neuronal damage. DJ-1 knockout mice demonstrated increased vulnerability in vivo to 6-hydroxydopamine (6-OHDA) hemiparkinsonian PD model. Astrocytes isolated from DJ-1 knockout mice showed an inferior ability to protect human neuroblastoma cells against 6-OHDA insult both by co-culture and through their conditioned media, as compared to wild-type astrocytes. DJ-1 knockout astrocytes showed blunted ability to increase the expression of cellular protective mechanisms against oxidative stress mediated via Nrf-2 and HO-1 in response to exposure to 6-OHDA. These experiments demonstrated that lack of DJ-1 impairs astrocyte-mediated neuroprotection.

Keywords

Parkinson’s disease DJ-1 6-hydroxydopamine 

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Nirit Lev
    • 1
    • 2
  • Yael Barhum
    • 1
  • Tali Ben-Zur
    • 1
  • Eldad Melamed
    • 2
  • Israel Steiner
    • 2
  • Daniel Offen
    • 1
  1. 1.The Neuroscience Laboratory, Felsenstein Medical Research Center, Sackler School of MedicineTel-Aviv UniversityPetah-TikvaIsrael
  2. 2.Department of Neurology, FMRC, Rabin Medical CenterTel Aviv UniversityPetah-TikvaIsrael

Personalised recommendations