Increased PARP Expression in the Brain in Sporadic Amyotrophic Lateral Sclerosis

Abstract

Background & Objectives : Overactivation 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 sporadic amyotrophic lateral sclerosis (sALS), predominantly in cells with astroglial morphology. Method : In the present study, we evaluated whether the PARP expression was present widespread in other regions of brain tissue including motor cortex, parietal cortex and cerebellum. Results : By western blot, PARP IR in motor cortex from sALS patients compared to age-matched 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 controls, in regions which are usually clinically unaffected in ALS (p=0.043, p=0.035, respectively). Immunohistochemistry revealed that PARP staining was more prominent in the cortical neurons and in the subcortical white matter glial cells from sALS patients compared to disease controls. Conclusion : 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