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Updated: Jul 8, 2026

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Quantitative Analysis of Alternative Pre-mRNA Splicing in Mouse Brain Sections Using RNA In Situ Hybridization Assay
Published on: August 26, 2018
Estrogen receptor-alpha splice variants in the human brain
Tatjana A Ishunina1, Dick F Swaab
1Department of Histology and Embryology, Kursk State Medical University, Kursk, Russia. t.ishunina@nin.knaw.nl
Summary
Altered estrogen receptor-alpha (ERalpha) splice variants in the human brain are linked to aging and Alzheimer's disease (AD). Understanding these variants is crucial for effective estrogen therapy in neurological conditions.
Area of Science:
- Neuroscience
- Molecular Biology
- Endocrinology
Background:
- Estrogen receptor-alpha (ERalpha) plays a key role in brain function.
- ERalpha signaling is implicated in aging and Alzheimer's disease (AD).
- The role of ERalpha splice variants in the brain remains incompletely understood.
Purpose of the Study:
- To review recent findings on ERalpha splice variants in the aging and AD human brain.
- To highlight the brain area-specific expression patterns of these variants.
- To discuss the implications for estrogen's effects on the brain and estrogen therapy.
Main Methods:
- Analysis of mRNA and protein levels of ERalpha splice variants.
- Comparison of variant expression in different brain regions (e.g., mamillary body, hippocampus).
- Investigation of age-related and AD-related changes in variant expression.
Main Results:
- Various ERalpha splice variants show altered levels in the aging and AD human brain.
- Expression patterns are brain area-specific, with different isoforms predominant in the mamillary body (del.7) and hippocampus (del.4).
- Specific variants (e.g., del.7/2) decline with age in the mamillary body, while others are unaffected in the hippocampus. A novel MB1 isoform accumulates in postmenopausal women.
Conclusions:
- ERalpha splice variants are significantly altered in the aging and AD brain.
- Brain region-specific expression and changes in these variants are critical.
- Considering ERalpha splice variants is essential for understanding estrogen's role in the brain and optimizing estrogen therapy for neurological disorders.
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