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Gestational high fat diet protects 3xTg offspring from memory impairments, synaptic dysfunction, and brain pathology

Abstract

Maternal history for sporadic Alzheimer’s disease (AD) predisposes the offspring to the disease later in life. However, the mechanisms behind this phenomenon are still unknown. Lifestyle and nutrition can directly modulate susceptibility to AD. Herein we investigated whether gestational high fat diet influences the offspring susceptibility to AD later in life. Triple transgenic dams were administered high fat diet or regular chow throughout 3 weeks gestation. Offspring were fed regular chow throughout their life and tested for spatial learning and memory, brain amyloidosis, tau pathology, and synaptic function. Gestational high fat diet attenuated memory decline, synaptic dysfunction, amyloid-β and tau neuropathology in the offspring by transcriptional regulation of BACE-1, CDK5, and tau gene expression via the upregulation of FOXP2 repressor. Gestational high fat diet protects offspring against the development of the AD phenotype. In utero dietary intervention could be implemented as preventative strategy against AD.

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Acknowledgements

Special thanks to Dr Margaret Sperow and Dr Lynn Kirby for technical assistance in the electrophysiology experiments, and to Dr Peter Davies for providing the MC1 antibody. DP is the Scott Richards North Star Charitable Foundation Chair for Alzheimer’s Research. This study was supported in part by grants from the National Institute of Health (AG060711), and the Scott Richards North Star Charitable Foundation.

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ADM and DP designed the study. ADM, EL, and MEC performed the experiments. JJ, J-PJI and ADM designed and performed the methylation studies. ADM and DP wrote the paper. All authors have discussed the results and seen the final version of the paper before submission.

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Correspondence to Domenico Praticò.

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Di Meco, A., Jelinek, J., Lauretti, E. et al. Gestational high fat diet protects 3xTg offspring from memory impairments, synaptic dysfunction, and brain pathology. Mol Psychiatry (2019). https://doi.org/10.1038/s41380-019-0489-y

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