Effects of Estrogen on Beta-Amyloid-Induced Cholinergic Cell Death in the Nucleus Basalis Magnocellularis

• DOI: 10.1159/000321119
• Publication Date: 2010-10-11T07:07:01Z
• Authors: Éva M. Szegő; Attila Csorba; Tamás Janáky; Katalin A. Kékesi; István M. Ábrahám; Gábor M. Mórotz; Botond Penke; Miklós Palkovits; Ünige Murvai; Miklós S.Z. Kelle...; József Kardos; Gábor D. Juhász
• Keywords: Nucleus basalis

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