DJ-1 knock-down in astrocytes impairs astrocyte-mediated neuroprotection against rotenone

• Published in: Neurobiology of disease 2009-01, Vol.33 (1), p.28-36
• Main Authors: Mullett, Steven J, Hinkle, David A
• Format: Article
• Language: English
• Subjects: Animals; Astrocyte; Astrocytes - physiology; Blotting, Western; Cell Survival; Cells, Cultured; Coculture Techniques; DJ-1; Gene Knockdown Techniques; Glia; Immunohistochemistry; Mice; Neurology; Neurons - drug effects; Neurons - physiology; Neuroprotection; Oncogene Proteins - genetics; Oncogene Proteins - metabolism; PARK7; Parkinson's disease; Peroxiredoxins; Protein Deglycase DJ-1; RNA, Small Interfering - metabolism; Rotenone; Rotenone - toxicity; siRNA; Transfection
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2008.09.013

Abstract Mutations that eliminate DJ-1 expression cause a familial form of Parkinson's disease (PD). In sporadic PD, and many other neurodegenerative diseases, reactive astrocytes over-express DJ-1 whereas neurons maintain its expression at non-disease levels. Since DJ-1 has neuroprotective properties, and since astrocytes are known to support and protect neurons, DJ-1 over-expression in reactive astrocytes may reflect an attempt by these cells to protect themselves and surrounding neurons against disease progression. We used neuron–astrocyte contact and non-contact co-cultures to show that DJ-1 knock-down in astrocytes impaired their neuroprotective capacity, relative to wild-type astrocytes, against the neurotoxin rotenone. Conversely, DJ-1 over-expression in astrocytes augmented their neuroprotective capacity. Experiments using astrocyte conditioned media on neuron-only cultures suggested that astrocyte-released, soluble factors were involved in the DJ-1-dependent, astrocyte-mediated neuroprotective mechanism. Our findings support the developing view that astrocytic dysfunction, in addition to neuronal dysfunction, may contribute to the progression of a variety of neurodegenerative disorders.