Glia mediates the neuroprotective action of estradiol on β-amyloid-induced neuronal death

M. A. Sortino, M. Chisari, S. Merlo, C. Vancheri, M. Caruso, F. Nicoletti, P. L. Canonico, A. Copani

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Abstract

17β-Estradiol (17β-E2) is known to exert neuroprotective activity against β-amyloid, but its exact target and mechanism of action in this effect have not been elucidated. The involvement of astroglia in neuroprotection of 17β-E2 against the β-amyloid fragment [βAP(25-35)] has been evaluated using an experimental paradigm in which medium conditioned from rat astroglia pretreated with 17β-E2 was transferred to pure rat cortical neurons challenged with 25 μM βAP(25-35) for 24 h. The toxicity of βAP (26-35) was assessed by flow cytometry, evaluating the ability of the peptide to induce an aberrant mitotic cell cycle in neurons. The results obtained indicate that conditioned medium from astrocytes preexposed to 17β-E2 for 4 h increased the viability of cortical neurons treated with βAP(25-35). This effect was not modified by treatment with the estrogen receptor antagonist ICI 182,780, added directly to neurons, nor was it mimicked by direct addition of 17β-E2 to neuronal cultures during exposure to βAP(25-35). A soluble factor stimulated by 17β-E2 seemed to be involved, and accordingly, the intracellular and released levels of TGF-β1 were increased by 17β-E2 treatment, as established by Western blot analysis. In addition, the intracellular content of TGF-β1 in immunopositive cells, as detected by flow cytometry, was reduced, suggesting that 17β-E 2 stimulated mainly the release of the cytokine. In support of a role for TGF-β1 in astrocyte-mediated 17β-E2 neuroprotective activity, incubation with a neutralizing anti-TGF-β1 antibody significantly modified the reduction of neuronal death induced by 17β-E 2-treated astrocyte-conditioned medium.

Original languageEnglish
Pages (from-to)5080-5086
Number of pages7
JournalEndocrinology
Volume145
Issue number11
DOIs
Publication statusPublished - Nov 2004

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ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Sortino, M. A., Chisari, M., Merlo, S., Vancheri, C., Caruso, M., Nicoletti, F., Canonico, P. L., & Copani, A. (2004). Glia mediates the neuroprotective action of estradiol on β-amyloid-induced neuronal death. Endocrinology, 145(11), 5080-5086. https://doi.org/10.1210/en.2004-0973