PARP expression is increased in astrocytes but decreased in motor neurons in the spinal cord of sporadic ALS patients

Seung H. Kim, Jenny S. Henkel, David R. Beers, Ihsan S. Sengun, Ericka P. Simpson, J. Clay Goodman, J. Engelhardt, L. Siklós, Stanley H. Appel

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Abstract

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. Using Western analyses of postmortem tissue, we demonstrated that PARP-immunoreactivity (PARP-IR) was increased 3-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 controls. This result contrasts sharply to the staining of Alzheimer and MPTP-induced Parkinson diseased tissue, where poly(ADP-ribose) (PAR)-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. The present results demonstrate glial alterations in sALS spinal cord tissue and support the role of glial alterations in sALS pathogenesis. Additionally, these results demonstrate differences in sALS spinal motor neurons and astrocytes compared to brain neurons and astrocytes in Alzheimer disease and MPTP-induced Parkinson disease despite the presence of markers for oxidative stress in all 3 diseases.

Original languageEnglish
Pages (from-to)88-103
Number of pages16
JournalJournal of Neuropathology and Experimental Neurology
Volume62
Issue number1
Publication statusPublished - Jan 1 2003

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Poly(ADP-ribose) Polymerases
Motor Neurons
Astrocytes
Spinal Cord
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Amyotrophic Lateral Sclerosis
Staining and Labeling
Neuroglia
Parkinson Disease
Oxidative Stress
Poly Adenosine Diphosphate Ribose
Amyotrophic lateral sclerosis 1
Neurons
DNA Damage
Chromatin
Alzheimer Disease
Messenger RNA
Membranes
Brain

Keywords

  • Amyotrophic lateral sclerosis (ALS)
  • Astrocyte
  • Motor neuron
  • Poly(ADP-ribose) polymerase (PARP)
  • Reverse transcriptase-polymerase chain reaction (RT-PCR)
  • Western analysis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Kim, S. H., Henkel, J. S., Beers, D. R., Sengun, I. S., Simpson, E. P., Goodman, J. C., ... Appel, S. H. (2003). PARP expression is increased in astrocytes but decreased in motor neurons in the spinal cord of sporadic ALS patients. Journal of Neuropathology and Experimental Neurology, 62(1), 88-103.

PARP expression is increased in astrocytes but decreased in motor neurons in the spinal cord of sporadic ALS patients. / Kim, Seung H.; Henkel, Jenny S.; Beers, David R.; Sengun, Ihsan S.; Simpson, Ericka P.; Goodman, J. Clay; Engelhardt, J.; Siklós, L.; Appel, Stanley H.

In: Journal of Neuropathology and Experimental Neurology, Vol. 62, No. 1, 01.01.2003, p. 88-103.

Research output: Contribution to journalArticle

Kim, Seung H. ; Henkel, Jenny S. ; Beers, David R. ; Sengun, Ihsan S. ; Simpson, Ericka P. ; Goodman, J. Clay ; Engelhardt, J. ; Siklós, L. ; Appel, Stanley H. / PARP expression is increased in astrocytes but decreased in motor neurons in the spinal cord of sporadic ALS patients. In: Journal of Neuropathology and Experimental Neurology. 2003 ; Vol. 62, No. 1. pp. 88-103.
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