Sublethal dose of 4-hydroxynonenal reduces intracellular calcium in surviving motor neurons in vivo

Lóránd Vigh, R. Glenn Smith, Judit Soós, J. Engelhardt, Stanley H. Appel, L. Siklós

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

4-Hydroxynonenal (4-HNE), a major lipid peroxidation product, induces oxidative stress, acts as an autonomous effector of cell death in motor neuron hybrid cell cultures, and is elevated in the cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS). Elevation of the total intracellular calcium has also been demonstrated in motor axon terminals of ALS patients as well as in spinal motor neurons of animal models of familial and sporadic ALS. Since the association of intracellular calcium and oxidative stress has been suggested in ALS, the in vivo effect of intrathecally administered 4-HNE on the motor neuronal calcium level was examined in the spinal cord of rats. After 12 days of treatment, total intracellular calcium was assayed by electron microscopic histochemistry using the oxalate-pyroantimonate method. Morphology of spinal motor neurons was characterized by light and electron microscopy. In rats, 4-HNE treatment induced a mild impairment of gait, elevation of 4-HNE in the CSF, loss of spinal motor neurons, and reduction of total calcium in the surviving, structurally intact motor neurons. 4-HNE could only cause a lesion if glutathione synthesis was concomitantly inhibited in the animals. The results suggest that upstream components of the oxidative injury in relation to lipid peroxidation are necessary to compromise the glutathione system in ALS, allowing an increase of 4-HNE in the CSF, which further aggravates the primary oxidative lesion. The reduced intracellular calcium in the surviving motor neurons with no morphological features of degeneration may reflect an impaired ionic homeostasis, which may indicate a residual damage of an incomplete degenerative process.

Original languageEnglish
Pages (from-to)567-575
Number of pages9
JournalActa Neuropathologica
Volume109
Issue number6
DOIs
Publication statusPublished - Jun 2005

Fingerprint

Motor Neurons
Amyotrophic Lateral Sclerosis
Calcium
Cerebrospinal Fluid
Lipid Peroxidation
Glutathione
Oxidative Stress
Oxalates
Hybrid Cells
Presynaptic Terminals
Gait
4-hydroxy-2-nonenal
Spinal Cord
Electron Microscopy
Homeostasis
Cell Death
Animal Models
Cell Culture Techniques
Electrons
Light

Keywords

  • 4-Hydroxynonenal
  • Calcium
  • Degeneration
  • Motorneuron
  • Oxidative stress

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Sublethal dose of 4-hydroxynonenal reduces intracellular calcium in surviving motor neurons in vivo. / Vigh, Lóránd; Smith, R. Glenn; Soós, Judit; Engelhardt, J.; Appel, Stanley H.; Siklós, L.

In: Acta Neuropathologica, Vol. 109, No. 6, 06.2005, p. 567-575.

Research output: Contribution to journalArticle

Vigh, Lóránd ; Smith, R. Glenn ; Soós, Judit ; Engelhardt, J. ; Appel, Stanley H. ; Siklós, L. / Sublethal dose of 4-hydroxynonenal reduces intracellular calcium in surviving motor neurons in vivo. In: Acta Neuropathologica. 2005 ; Vol. 109, No. 6. pp. 567-575.
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