Effects of Estrogen on Beta-Amyloid-Induced Cholinergic Cell Death in the Nucleus Basalis Magnocellularis
| Autor: | Botond Penke, Miklós Palkovits, Ünige Murvai, Gábor M Mórotz, Éva M. Szegö, Tamás Janáky, Miklós S.Z. Kellermayer, József Kardos, Attila Csorba, Katalin A. Kékesi, István M. Ábrahám, Gábor Juhász |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Proteomics
MAPK/ERK pathway medicine.medical_specialty Microinjections medicine.drug_class Endocrinology Diabetes and Metabolism Biology Nucleus basalis Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Endocrinology Internal medicine medicine Animals Particle Size Cholinergic neuron 030304 developmental biology 0303 health sciences Amyloid beta-Peptides Cell Death Estradiol Endocrine and Autonomic Systems Neurodegeneration Protein phosphatase 1 Protein phosphatase 2 Alzheimer disease Estrogen Amyloid Micropunch MAPK pathway Differential two-dimensional gel electrophoresis Nucleus basalis magnocellularis medicine.disease 3. Good health Mice Inbred C57BL Neuroprotective Agents Cholinergic Fibers Basal Nucleus of Meynert Cholinergic Female 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Neuroendocrinology. 93:90-105 |
| ISSN: | 1423-0194 0028-3835 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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