Ceramide protects hippocampal neurons against excitotoxic and oxidative insults, and amyloid β-peptide toxicity

Yadong Goodman, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

The transcription factor NFκB is activated by various signals associated with brain injury, including tumor necrosis factor (TNF), oxidative insults, and amyloid β-peptide (Aβ). We recently reported that TNFs activate NFκB in neurons and protect them against excitotoxic and oxidative insults, including Aβ toxicity. We now report that C2-ceramide (C2), a membrane- permeant activator of NFκB, protects cultured rat hippocampal neurons against death induced by glutamate, FeSO4, and Aβ. Protection was concentration dependent, specific (a ceramide analogue known not to activate NFκB was ineffective), required pretreatment, and was blocked by inhibitors of RNA and protein synthesis. Lipid peroxidation and accumulation of cellular peroxides induced by glutamate, FeSO4, and Aβ were significantly attenuated in neurons pretreated with C2. The data indicate that C2 induces antioxidant pathways in neurons and suggest novel approaches for reducing neuronal injury in both acute and chronic neurodegenerative conditions.

Original languageEnglish (US)
Pages (from-to)869-872
Number of pages4
JournalJournal of Neurochemistry
Volume66
Issue number2
StatePublished - Feb 1996
Externally publishedYes

Fingerprint

Ceramides
Amyloid
Neurons
Toxicity
Peptides
Glutamic Acid
Nucleic Acid Synthesis Inhibitors
Protein Synthesis Inhibitors
Peroxides
Brain Injuries
Lipid Peroxidation
Rats
Brain
Transcription Factors
Tumor Necrosis Factor-alpha
Antioxidants
Membranes
Lipids
Wounds and Injuries

Keywords

  • Alzheimer's disease
  • Ceramide
  • Confocal laser scanning microscope imaging
  • Glutamate excitotoxicity
  • Lipid peroxidation
  • Neuron death
  • NFκB
  • Reactive oxygen species
  • Transcription factor

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Ceramide protects hippocampal neurons against excitotoxic and oxidative insults, and amyloid β-peptide toxicity. / Goodman, Yadong; Mattson, Mark P.

In: Journal of Neurochemistry, Vol. 66, No. 2, 02.1996, p. 869-872.

Research output: Contribution to journalArticle

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