PARP Expression is Increased in Astrocytes but Decreased in Motor Neurons in the Spinal Cord of Sporadic ALS Patients

Abstract

Background & Objectives : The evidence for increased oxidative stress and DNA damage in amyotrophic lateral sclerosis (ALS) prompted studies to determine if the expression of poly(ADP-ribose) polymerase (PARP) is increased in ALS. Method : Using western analyses of postmortem tissue, we demonstrated that PARP-immunoreactivity (PARP-IR) was increased three-fold in spinal cord tissues of sporadic ALS (sALS) patients compared with non-neurological disease controls. Results : Despite the increased PARP-IR, PARP mRNA expression was not increased significantly. Immunohistochemical analyses revealed PARP-IR was increased in both white and gray matter of sALS spinal cord. While PARP-IR was predominantly seen in astrocytes, large motor neurons displayed reduced staining compared with controls. This result contrasts sharply to the staining of Alzheimer’s and MPTP induced Parkinson’s diseased tissue, where PARP-IR was seen mostly in neurons, with little astrocytic staining. PARP-IR was increased in the pellet fraction of sALS homogenates compared with control homogenates, representing potential PARP binding to chromatin or membranes and suggesting a possible mechanism of PARP stabilization. Conclusion : The present results demonstrate glial alterations in sALS tissue and support the role of glial alterations in sALS pathogenesis. Additionally, these results demonstrate differences in sALS vs. Alzheimer’s and MPTP induced Parkinson’s diseases despite the presence of markers for oxidative stress in all three diseases.