Early‐life exposure to high‐fat diet influences brain health in aging mice

• Published in: Aging cell 2019-12, Vol.18 (6), p.e13040-n/a
• Main Authors: Di Meco, Antonio, Praticò, Domenico
• Format: Article
• Language: English
• Subjects: Aging; Aging - drug effects; Animals; Brain; Brain - drug effects; brain aging; Caspase; Diet; Diet, High-Fat - adverse effects; Disease susceptibility; Environmental factors; Epidemiology; Female; Fetuses; Gestation; Glucose Tolerance Test; Health aspects; High fat diet; Intrauterine exposure; Isoforms; Learning; Long-term effects; Male; Maze Learning - drug effects; memory; Mice; Nervous system diseases; Neurodegenerative diseases; Offspring; Original; Pregnancy; Prenatal Exposure Delayed Effects; synapse; tau pathology; Tau protein
• ISSN: 1474-9718; 1474-9726
• DOI: 10.1111/acel.13040

Epidemiological studies have suggested a link between exposure to environmental factors early in life and susceptibility to neurodegenerative diseases in adulthood. In the short term, maternal diet is important for the growth and development of the fetus; however, it may also have long‐term effects on the health status of the offspring. Here, we investigate the effect that maternal high‐fat diet during gestation has on brain health of the offspring later in life. B6129SF2/J dams were fed a high‐fat diet during the 3 weeks’ gestation, then switched to standard chow diet after delivery. Offspring were always fed regular diet for the entire study and assessed in learning, memory, and brain pathology when 18 months old. Compared with offspring from control mothers, the ones from mothers exposed to high‐fat diet had significant better performance in learning and memory tests, which associated with an amelioration of synaptic integrity. Additionally, they had a significant reduction in total tau, a decrease in its pathological conformational changes and lower levels of caspase‐3‐cleaved isoforms. Our findings demonstrate that in utero exposure to high‐fat diet plays a protective role for offspring brain health later in life. They support the novel hypothesis that targeted dietary intervention specifically restricted to the gestation period could be implemented as preventative strategy for the age‐dependent decline in brain health. In utero exposure to high fat diet by downregulating caspase‐3 activation in the central nervous system positively affects learning and memory, synapse integrity and neuropathology in the aging brain of the offspring.