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Gestational high fat diet protects 3xTg offspring from memory impairments, synaptic dysfunction, and brain pathology
Antonio Di Meco1, Jaroslav Jelinek2, Elisabetta Lauretti1
1Alzheimer's Center at Temple, Lewis Katz School of Medicine Temple University, Philadelphia, PA, USA.
Molecular Psychiatry
|August 28, 2019
Summary
Maternal high-fat diet during pregnancy surprisingly protects offspring from Alzheimer's disease (AD) later in life. This prenatal nutritional intervention improves memory and reduces AD brain pathology in offspring.
Area of Science:
- Neuroscience
- Genetics
- Nutritional Science
Background:
- Maternal history of Alzheimer's disease (AD) increases offspring risk.
- Mechanisms linking maternal factors to offspring AD susceptibility are unclear.
- Lifestyle and nutrition influence AD development.
Purpose of the Study:
- To investigate if a gestational high-fat diet affects offspring's later-life susceptibility to AD.
- To explore the underlying molecular mechanisms of this influence.
Main Methods:
- Triple transgenic mice dams were fed a high-fat diet or regular chow during gestation.
- Offspring were maintained on a regular diet and assessed for cognitive function, amyloid-β and tau pathology, and synaptic function.
- Gene expression analysis focused on BACE-1, CDK5, and tau, involving the FOXP2 repressor.
Main Results:
- Gestational high-fat diet significantly attenuated memory decline and synaptic dysfunction in offspring.
- Reduced amyloid-β and tau neuropathology were observed in offspring exposed to the maternal high-fat diet.
- This protection was linked to transcriptional regulation via FOXP2 repressor upregulation, affecting BACE-1, CDK5, and tau gene expression.
Conclusions:
- Maternal high-fat diet during gestation offers protection against the development of Alzheimer's disease phenotype in offspring.
- In utero dietary interventions represent a potential preventative strategy for AD.
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