title: DJ-1 immunoreactivity in human brain astrocytes is dependent on infarct presence and infarct age.
abstract: DJ-1 is a protein with anti-oxidative stress and anti-apoptotic properties that is abundantly expressed in reactive CNS astrocytes in chronic neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and Pick's disease. Genetic mutations which eliminate DJ-1 expression in humans are sufficient to produce an early-onset form of familial PD, PARK7, suggesting that DJ-1 is a critical component of the neuroprotective arsenal of the brain. Previous studies in parkinsonism/dementia brain tissues have revealed that reactive astrocytes within and surrounding incidentally identified infarcts were often robustly immunoreactive for DJ-1, especially if the infarcts showed histological features consistent with older age. Given this, we sought to evaluate astrocytic DJ-1 expression in human stroke more extensively, and with a particular emphasis on determining whether immunohistochemical DJ-1 expression in astrocytes correlates with histological infarct age. The studies presented here show that DJ-1 is abundantly expressed in reactive infarct region astrocytes in both gray and white matter, that subacute and chronic infarct region astrocytes are much more robustly DJ-1+ than are acute infarct and non-infarct region astrocytes, and that DJ-1 staining intensity in astrocytes generally correlates with that of the reactive astrocyte marker GFAP. Confocal imaging of DJ-1 and GFAP dual-labelled human brain sections were used to confirm the localization to and expression of DJ-1 in astrocytes. Neuronal DJ-1 staining was minimal under all infarct and non-infarct conditions. Our data support the conclusion that the major cellular DJ-1 response to stroke in the human brain is astrocytic, and that there is a temporal correlation between DJ-1 expression in these cells and advanced infarct age.
authors.affiliation: Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Mullett
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hamilton
authors.forename: David A
authors.initials: DA
authors.lastname: Hinkle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D020520:Brain Infarction / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1; D020521:Stroke; D013997:Time Factors; D055815:Young Adult
chemical_list: D005904:Glial Fibrillary Acidic Protein; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1