Amyloid-β peptide activates cultured astrocytes: Morphological alterations, cytokine induction and nitric oxide release

Jingru Hu, Keith T. Akama, Grant A. Krafft, Brett A. Chromy, Linda J. Van Eldik

Research output: Contribution to journalArticlepeer-review

285 Scopus citations

Abstract

A common feature of many neurodegenerative disorders is an abundance of activated glial cells (astrocytes and microglia). In Alzheimer's disease (AD), activated astrocytes are in close apposition to and surrounding the amyloid plaques. The mechanisms by which the astrocytes become activated in AD and the consequences of reactive astrocytosis to disease progression are not known. We examined the possibility that the amyloid-β (A β) peptide, a major constituent of the amyloid plaque, could act as a stimulus leading to activation. We found that treatment of rat cortical astrocyte cultures with aggregated A β 1-42 peptide induces activation, as assessed by reactive morphological changes and upregulation of selective glial mRNA and proteins, such as the inflammatory cytokine interleukin-1 β. A β also stimulates inducible nitric oxide synthase (iNOS) mRNA levels and nitric oxide (NO) release. A β 1-42, a major form of amyloid associated with neurotoxicity, activated astrocytes in a time- and dose-dependent manner, whereas a scrambled A β 1-42 sequence or A β 17-42 had little or no effect. We also determined that the A β activity can be found in a supernatant fraction containing soluble A β oligomers. Our data suggest that A β plays a role in the reactive astrocytosis of AD and that the inflammatory response induced upon glial activation is a critical component of the neurodegenerative process.

Original languageEnglish
Pages (from-to)195-206
Number of pages12
JournalBrain Research
Volume785
Issue number2
DOIs
StatePublished - Mar 2 1998

Bibliographical note

Funding Information:
These studies were supported in part by NiH grants AG13939 (to LVE) AG13496 (to GAK) and AG15501 (to GAK and LVE). We thank Drs. D.M. Watterson, T.J. Lukas, U. Slomcznska, L.M. Zhou, and C. Edwards for assistance with peptide production, and Dr. E. Turkington for assistance with astrocyte cultures.

Keywords

  • Alzheimer's disease
  • Astrocyte
  • Beta amyloid
  • Interleukin-1
  • Nitric oxide synthase

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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