Effects of estrogen on beta-amyloid-induced cholinergic cell death in the nucleus basalis magnocellularis
Open accessAbstract
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.
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The therapeutic properties of phytoestrogen support evidence in prevention of Alzheimer's disease.
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From Phytotherapy: A promising approach for the treatment of Alzheimer's disease (2022) · cites this paper as [74]
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Research works printed but not linked: 1
- Hernandez CM, Kayed R, Zheng H, Sweatt JD, Dineley KT: Loss of alpha 7 nicotinic re- ceptors enhances beta-amyloid oligomer ac- cumulation, exacerbating early-stage cogni- tive decline and septohippocampal pathol- ogy in a mouse model of Alzheimer's dis- ease. J Neurosci 2010; 30: 2442-2453.
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Phytotherapy: A promising approach for the treatment of Alzheimer's disease
John, O. O., Amarachi, I. S., Chinazom, A. P., Adaeze, E., Kale, M. B., Umare, M. D., & Upaganlawar, A. B. (2022) · Pharmacological Research - Modern Chinese Medicine · doi:10.1016/j.prmcm.2021.100030 · Cited by 69 · see citing works
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- Authors
- Szegő, É. M., Csorba, A., Janáky, T., Kékesi, K. A., Ábrahám, I. M., Mórotz, G. M., Penke, B., Palkovits, M., Murvai, Ü., Kellermayer, M. S. Z., Kardos, J., & Juhász, G. D.
- Affiliations
- Eötvös Loránd University (HU)
- University of Szeged (HU)
- Semmelweis University (HU)
- ORCID
- Venue
- Neuroendocrinology
- Publisher
- S. Karger AG
- Published
- 2010-10-08
- Volume
- 93
- Issue
- 2
- Pages
- 90-105
- ISSN
- 0028-3835 (ISSN-L)
- 1423-0194
- OpenAlex
- W2048473457
- Cited by
- 24
- References
- 79
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2018: 1 · 2016: 2 · 2015: 3 · 2014: 1 · 2013: 2 · 2012: 4
- FWCI
- 2.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- SZTE Publicatio Repozitórium (University of Szeged) (acceptedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- GRO (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft
- Hungarian Scientific Research Fund (68464, 81950)
- Szegedi Tudományegyetem
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- estrogen, amyloid-beta, cholinergic neurodegeneration, nucleus basalis magnocellularis, Alzheimer's disease, estrogen pretreatment, amyloid-beta oligomers, mitochondrial dysfunction, MAPK signaling, nitric oxide, ovariectomy, proteomics, neuroprotection
- MeSH terms
- Animals, Cholinergic Fibers, Estradiol, Female, Mice, Inbred C57BL, Microinjections, Particle Size, Signal Transduction, Amyloid beta-Peptides, Cell Death, Neuroprotective Agents, Basal Nucleus of Meynert, Proteomics, Mice
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