BACKGROUND: 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: Twenty Spinal cord specimens were obtained at the autopsy of sALS patients (n=11) and age-matched controls with non-neurological diseases (n=9). RESULTS: 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. 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 the controls. PARP-IR was increased in the pellet fraction of sALS homogenates compared with the control homogenates, representing potential PARP binding to chromatin or membranes and suggesting a possible mechanism of PARP stabilization. CONCLUSIONS: The present results demonstrate glial alterations in sALS tissue and support the role of glial alterations in sALS pathogenesis.
Amyotrophic Lateral Sclerosis* ; Astrocytes* ; Autopsy ; Chromatin ; DNA Damage ; Humans ; Membranes ; Motor Neurons* ; Oxidative Stress ; RNA, Messenger ; Spinal Cord*