Increased Neuronal and Glial Poly (ADP-Ribose) Polymerase Immunoreactivity in the Brain of Sporadic Amyotrophic Lateral Sclerosis

Background : Over activation of the DNA repairing enzyme, poly (ADP-ribose) polymerase (PARP) in response to oxidative damage of DNA appears to play a role in cellular death in neurodegenerative diseases. Previous data suggested that PARP immunoreactivity (IR) was increased in the white and gray matter in spinal cord of the sporadic amyotrophic lateral sclerosis (sALS), predominantly in cells with astroglial morphology. Methods : In the present study, we evaluated whether the PARP expression was present widespread in various regions of brain tissue including the motor cortex, parietal cortex and cerebellum. Results : By western blot, PARP-IR in motor cortex from sALS patients, compared to the same region from age-matched normal controls, was also significantly increased (p=0.006). Importantly, PARP-IR was also increased in the parietal cortex, and cerebellum of sALS patients compared to the controls, in regions that are usually clinically unaffected in ALS (p=0.043, p=0.035, respectively). In addition, increased PARP expression in ALS was more prominent compared to Alzheimer’s brain. Immunohistochemistry revealed that PARP staining was more significant in the cortical neurons and in the subcortical white matter glial cells from sALS patients compared to normal controls and Alzheimer’s disease. Conclusions : The data demonstrate that increase in PARP-IR is not limited only to the vulnerable motor cortex. Furthermore, PARP-IR is present in both cortical neuronal and subcortical glial cells. The data suggest that widespread cellular stress on neuronal and glial cells is present in the brain of sporadic ALS patients. J Korean Neurol Assoc 20(6):682~693, 2002