DJ-1 immunoreactivity in human brain astrocytes is dependent on infarct presence and infarct age

• Published in: Neuropathology 2009-04, Vol.29 (2), p.125-131
• Main Authors: Mullett, Steven J., Hamilton, Ronald L., Hinkle, David A.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Analysis of Variance; astrocyte; Astrocytes - metabolism; Astrocytes - pathology; Brain - metabolism; Brain - pathology; Brain Infarction - metabolism; Brain Infarction - pathology; DJ-1; Female; Fluorescent Antibody Technique; GFAP; Glial Fibrillary Acidic Protein - metabolism; Humans; Immunohistochemistry; infarct; Intracellular Signaling Peptides and Proteins - metabolism; Male; Microscopy, Confocal; Middle Aged; Neurons - metabolism; Oncogene Proteins - metabolism; Protein Deglycase DJ-1; Stroke; Time Factors; Young Adult
• ISSN: 0919-6544; 1440-1789
• DOI: 10.1111/j.1440-1789.2008.00955.x

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.