Ramirez G, Toro R, Dobeli H, von Bernhardi R.

Faculty of Medicine, Department of Neurology, Pontificia Universidad
Catolica de Chile, Marcoleta 391, Santiago, Chile; Faculty of Medicine,
Universidad de los Andes, Santiago, Chile.

The brain of Alzheimer's disease patients shows abundant dystrophic
neurites in close proximity to fibrillar beta-amyloid (Abeta) plaques,
and activated glial cells. We evaluated the influence of
pro-inflammatory molecules (LPS + IFN-gamma) on Abeta(1-42)
neurotoxicity. 2 muM Abeta(1-42) induced apoptosis of hippocampal cells
and LPS + IFN-gamma reduced the apoptosis induced by Abeta. However,
LPS + IFN-gamma prevented apoptosis only in hippocampal cultures
containing astrocytes. Also, LPS + IFN-gamma induced the secretion of
TGFbeta, a cytokine having neuroprotective effects, only in hippocampal
cultures that contained astrocytes. Astrocytes had a regulatory effect
over microglial and neuronal responses to Abeta. The results suggest
that LPS + IFN-gamma, traditionally considered as pro-apoptotic,
reduced apoptosis induced by Abeta through the activation of
neuroprotective mechanisms mediated by astrocytes. We propose that
astrocytes are pivotal in the modulation of inflammation of the CNS.
The impairment of the regulatory functions performed by activated
astrocytes could represent an important pathogenic mechanism for
neurodegenerative diseases.