Effects of estrogen on beta-amyloid-induced cholinergic cell death in the nucleus basalis magnocellularis

Éva M. Szego, Attila Csorba, Tamás Janáky, Katalin A. Kékesi, István M. Ábrahám, Gábor M. Mórotz, Botond Penke, Miklós Palkovits, Ünige Murvai, Miklós S.Z. Kellermayer, József Kardos, Gábor D. Juhász

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Alzheimer disease is characterized by accumulation of β-amyloid (Aβ) and cognitive dysfunctions linked to early loss of cholinergic neurons. As estrogen-based hormone replacement therapy has beneficial effects on cognition of demented patients, and it may prevent memory impairments, we investigated the effect of estrogen-pretreatment on Aβ-induced cholinergic neurodegeneration in the nucleus basalis magnocellularis (NBM). We tested which Aβ species induces the more pronounced cholinotoxic effect in vivo. We injected different Aβ assemblies in the NBM of mice, and measured cholinergic cell and cortical fiber loss. Spherical Aβ oligomers had the most toxic effect. Pretreatment of ovariectomized mice with estrogen before Aβ injection decreased cholinergic neuron loss and partly prevented fiber degeneration. By using proteomics, we searched for proteins involved in estrogen-mediated protection and in Aβ toxicity 24 h following injection. The change in expression of, e.g., DJ-1, NADH ubiquinone oxidoreductase, ATP synthase, phosphatidylethanolamine-binding protein 1, protein phosphatase 2A and dimethylarginine dimethylaminohydrolase 1 support our hypothesis that Aβ induces mitochondrial dysfunction, decreases MAPK signaling, and increases NOS activation in NBM. On the other hand, altered expression of, e.g., MAP kinase kinase 1 and 2, protein phosphatase 1 and 2A by Aβ might increase MAPK suppression and NOS signaling in the cortical target area. Estrogen pretreatment reversed most of the changes in the proteome in both areas. Our experiments suggest that regulation of the MAPK pathway, mitochondrial pH and NO production may all contribute to Aβ toxicity, and their regulation can be prevented partly by estrogen pretreatment.

Original languageEnglish
Pages (from-to)90-105
Number of pages16
JournalNeuroendocrinology
Volume93
Issue number2
DOIs
Publication statusPublished - Mar 1 2011

Keywords

  • Alzheimer disease
  • Amyloid
  • Differential two-dimensional gel electrophoresis
  • Estrogen
  • MAPK pathway
  • Micropunch
  • Nucleus basalis magnocellularis
  • Proteomics

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Effects of estrogen on beta-amyloid-induced cholinergic cell death in the nucleus basalis magnocellularis'. Together they form a unique fingerprint.

  • Cite this