Core Concepts
Maternal choline supplementation can improve cognitive function, neuronal hyperexcitability, and neuronal markers in a mouse model of Alzheimer's disease, while low choline levels can have adverse effects.
Abstract
The study investigated the effects of maternal choline supplementation (MCS) on cognitive function, neuronal hyperexcitability, and neuronal markers in a mouse model of Alzheimer's disease (AD), the Tg2576 mouse. Tg2576 breeding pairs were fed diets with low, intermediate, or high choline concentrations, and the offspring were then tested.
Key findings:
Offspring of mice fed the high choline diet showed reduced interictal spike (IIS) frequency, decreased granule cell ΔFosB expression (a marker of neuronal hyperexcitability), and restored NeuN expression (a neuronal marker) in the dentate gyrus. These mice also exhibited improved spatial memory performance.
In contrast, offspring exposed to the low choline diet had increased mortality, the weakest hilar NeuN immunoreactivity, and the greatest granule cell ΔFosB expression, although their IIS frequency was surprisingly low.
The intermediate choline diet did not prevent cognitive deficits or neuronal changes in Tg2576 mice.
The high choline diet improved object location memory in both wild-type and Tg2576 mice at 3 and 6 months of age, while the low and intermediate choline diets impaired performance.
The high choline diet also led to increased time spent exploring objects during the behavioral tasks, which may have contributed to the improved memory.
These results provide evidence that a diet high in choline early in life can improve outcomes in an AD mouse model, while low choline can have mixed effects. This is the first study to demonstrate that dietary choline can regulate hyperexcitability, hilar neurons, ΔFosB, and spatial memory in an AD animal model.
Stats
Tg2576 mice exposed to the high choline diet showed reduced interictal spike (IIS) frequency compared to those fed the low or intermediate choline diets.
Tg2576 mice exposed to the high choline diet had decreased granule cell ΔFosB expression compared to those fed the low choline diet.
Tg2576 mice exposed to the high choline diet had restored NeuN expression in the dentate gyrus hilus compared to those fed the low or intermediate choline diets.
Tg2576 mice exposed to the low choline diet had increased mortality compared to those fed the high choline diet.
Quotes
"In offspring of mice fed the high choline diet, IIS frequency declined, GC ΔFosB expression was reduced, and NeuN expression was restored."
"In contrast, offspring exposed to the relatively low choline diet had several adverse effects, such as increased mortality. They had the weakest hilar NeuN immunoreactivity and greatest GC ΔFosB protein expression."