Estrogen blocks neurotoxic effects of β-amyloid (1–42) and induces neurite extension on B103 cells

doi:10.1016/S0304-3940(97)00632-0

Neuroscience Letters

Volume 235, Issue 3, 17 October 1997, Pages 101-104

https://doi.org/10.1016/S0304-3940(97)00632-0 Get rights and content

Abstract

Clinical studies have shown that estrogen replacement therapy is associated with reduced risk of Alzheimer's disease (AD). We tested whether or not estrogen blocks neurotoxic effects of β-amyloid (1–42) (Aβ_1–42) on cultured B103 cells. Aβ_1–42 (1 μM) induced typical necrotic cell death, as revealed by light and electron microscopic examinations. Co-administration of estrogen not only blocked Aβ_1–42 toxicity to a large degree, but also enhanced neurite extension. Pretreatment with estrogen was even more effective in blocking Aβ_1–42 toxicity. When added 18 h after the beginning of Aβ_1–42 treatment, estrogen was still effective in halting the progress of cell death and enhancing neurite extension. The protection against Aβ_1–42-induced neuronal death by estrogen was unlikely due to a blockade of lipid peroxidation injury, since estrogen completely failed to attenuate ferrous chloride-induced cell death. These results demonstrate that estrogen blocks Aβ_1–42-induced neurotoxicity and enhances neurite extension on B103 cells, both of which may well be underlying mechanisms of beneficial effects of estrogen in AD.

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Acknowledgements

We thank Dr. Jay Young Koh for helpful comments on the initial manuscript, Dr. Byung Joo Gwag for helpful discussions regarding cell death and Dr. David Schubert for sharing B103 cells. This work was supported by Dementia Research Grant from Dae Woo Foundation, academic research fund of Ministry of Education, Republic of Korea (GE 97–#94), and Kyunggi Pharmaceutical Research Center grant.

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Citation Excerpt :
Elevated estrogen levels are associated with decreased neuron death in vivo and in vitro (Simpkins and Singh, 2008; Singh et al., 2006). In cell culture models, estrogens are neuroprotective against a variety of insults, including serum starvation (Bishop and Simpkins, 1994; Green et al., 1997a, 1997b), oxygen–glucose deprivation (Regan and Guo, 1997; Wilson et al., 2000), oxidative stress (Behl et al., 1995; Goodman et al., 1996), excitotoxicity (Goodman et al., 1996; Singer et al., 1996; Zaulyanov et al., 1999), β-amyloid peptides (Behl et al., 1995; Goodman et al., 1996; Green et al., 1996; Mook-Jung et al., 1997; Pike, 1999), iron toxicity (Goodman et al., 1996; Blum-Degen et al., 1998), hemoglobin (Regan and Guo, 1997), and mitochondrial toxins (Wang et al., 2001; De Girolamo et al., 2001; Regan and Guo, 1997). However, estrogen effects seem to depend on the type of neuronal tissue and injury model (apoptotic or necrotic) used (Harms et al., 2001; Kajta et al., 2004).
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Estrogen blocks neurotoxic effects of β-amyloid (1–42) and induces neurite extension on B103 cells

Abstract

Section snippets

Acknowledgements

Brain Res.

Biochem. Biophys. Res. Commun.

Neurosci. Lett.

J. Biol. Chem.

Neurochem. Int.

Trends Neurosci.

Lancet

Regulation and expression of the Alzheimer's beta/A4 amyloid protein precursor in health, disease, and Down's syndrome

Ann. N. Y. Acad. Sci.