Selective Enrichment of DJ-1 Protein in Primate Striatal Neuronal Processes: Implications for Parkinson's Disease

• Authors: James A. Olzmann, Emory University; Jill R. Bordelon, Emory University; E Christopher Muly, Emory University; Howard D Rees III, Emory University; Allan I Levey, Emory University; Lian Li, Emory University; Lih-Shen Chin, Emory University
• Journal Title: Journal of Comparative Neurology
• Volume: Volume 500, Number 3
• Publisher: Wiley: 12 months | 2007-01-20, Pages 585-599
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/cne.21191
• Subjects: Biology, Neuroscience
• Keywords: PARK7; substantia nigra; striatum; electron microscopy; primate brain; distribution

Abstract

Mutations in DJ-1 cause autosomal recessive, early-onset Parkinson's disease (PD). The precise function and distribution of DJ-1 in the central nervous system remain unclear. In this study, we performed a comprehensive analysis of DJ-1 expression in human, monkey, and rat brains using antibodies that recognize distinct, evolutionarily conserved epitopes of DJ-1. We found that DJ-1 displays region-specific neuronal and glial labeling in human and non-human primate brain, sharply contrasting the primarily neuronal expression pattern observed throughout rat brain. Further immunohistochemical analysis of DJ-1 expression in human and non-human primate brains showed that DJ-1 protein is expressed in neurons within the substantia nigra pars compacta and striatum, two regions critically involved in PD pathogenesis. Moreover, immunoelectron microscopic analysis revealed a selective enrichment of DJ-1 within primate striatal axons, presynaptic terminals, and dendritic spines with respect to the DJ-1 expression in prefrontal cortex. Together, these findings indicate neuronal and synaptic expression of DJ-1 in primate subcortical brain regions and suggest a physiological role for DJ-1 in the survival and/or function of nigral-striatal neurons.