| Summary: | The brain of Alzheimer's disease patients shows abundant dystrophic neurites in close proximity to fibrillar β-amyloid (Aβ) plaques, and activated glial cells. We evaluated the influence of pro-inflammatory molecules (LPS + IFN-γ) on Aβ1–42 neurotoxicity. 2 μM Aβ1–42 induced apoptosis of hippocampal cells and LPS + IFN-γ reduced the apoptosis induced by Aβ. However, LPS + IFN-γ prevented apoptosis only in hippocampal cultures containing astrocytes. Also, LPS + IFN-γ induced the secretion of TGFβ, a cytokine having neuroprotective effects, only in hippocampal cultures that contained astrocytes. Astrocytes had a regulatory effect over microglial and neuronal responses to Aβ. The results suggest that LPS + IFN-γ, traditionally considered as pro-apoptotic, reduced apoptosis induced by Aβ 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.
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