Estradiol regulates APP mRNA alternative splicing in the mice brain cortex

Area of Science:

• Neuroscience
• Molecular Biology
• Endocrinology

Background:

• Alzheimer's disease (AD) is a neurodegenerative disorder associated with amyloid precursor protein (APP) gene.
• Alternative splicing of APP mRNA produces different protein isoforms, with APP695 being predominant in the brain.
• Hormonal factors, including sex steroids, are known to influence APP splicing and processing.

Purpose of the Study:

• To investigate the effects of sex steroid hormone withdrawal and administration on APP mRNA alternative splicing in aging mice.
• To determine the role of estradiol in modulating APP mRNA isoform levels during aging.

Main Methods:

• Studied APP mRNA alternative splicing in the brain cortex of male and female mice of different ages.
• Administered and withdrew sex steroid hormones (gonadectomy and estradiol supplementation).
• Quantified the levels of APP695 mRNA isoform using molecular biology techniques.

Main Results:

• APP695 mRNA levels were higher in adult mice compared to old mice.
• Gonadectomy altered APP695 mRNA levels, with an upregulation in most groups but a downregulation in adult females.
• Estradiol supplementation generally upregulated APP695 mRNA, except in old males.

Conclusions:

• APP695 mRNA levels change with age in mice.
• Sex steroid hormones, particularly estradiol, significantly modulate APP mRNA splicing.
• Estradiol's role in regulating APP mRNA isoforms suggests a potential link to Alzheimer's disease development.