Opposite effects of TGF-β1 on rapidly-and slowly-triggered excitotoxic injury

Jochen H M Prehn, Richard J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Transforming growth factor-β (TGF-β) has been shown to protect central neurons against diverse metabolic and excitotoxic challenges. We induced different types of excitotoxic injury on cultured rat hippocampal neurons and investigated TGF-β1 for its protective activity. TGF-β1 (0.3-10 ng/ml) effectively blocked excitotoxic injury of cultured rat hippocampal neurons induced by short-term exposure to the selective agonist N-methyl-D-aspartate (NMDA; 100 μM, 20 min). Excitotoxic injury caused by long-term exposure to the non-NMDA agonists kainate (50 μM, 24 hr) or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA; 10 μM, 24 hr) caused a similar reduction in neuronal viability. However, treatments with TGF-β1 (0.1-10 ng/ml) actually potentiated this slowly-triggered excitotoxic injury. Cultures of rat cerebellar neurons enriched for Purkinje cells have been shown to express AMPA/kainate receptors with significant permeability to Ca2+ and to be uniquely sensitive to non-NMDA receptor-mediated neurotoxicity. In this culture system, short-term exposure to kainate (100μM; 30min) in Na+-free extracellular solution caused a pronounced decrease in neuronal viability, and this toxicity was also significantly reduced in cultures treated with TGF-β1 (10 ng/ml). These results suggest that TGF-β1 has the capacity to protect neurons against rapidly-triggered, Ca2+-mediated excitotoxic injury, but significantly potentiates slowly-triggered types of excitotoxic injury. This complex action of TGF-β1 could have important implications for the use of TGF-βs and related growth factors in the treatment of neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)249-256
Number of pages8
JournalNeuropharmacology
Volume35
Issue number3
DOIs
StatePublished - Mar 1996

Keywords

  • Cytokine
  • Excitotoxicity
  • Kainate
  • N-Methyl-D-aspartate (NMDA)
  • Neuroprotection

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Fingerprint

Dive into the research topics of 'Opposite effects of TGF-β1 on rapidly-and slowly-triggered excitotoxic injury'. Together they form a unique fingerprint.

Cite this