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Perinatal choline supplementation prevents learning and memory deficits and reduces brain amyloid Aβ42 deposition in AppNL-G-F Alzheimer's disease model mice.

ABSTRACT: Alzheimer's disease (AD) is characterized by cognitive and memory impairments and neuropathological abnormalities. AD has no cure, inadequate treatment options, and a limited understanding of possible prevention measures. Previous studies have demonstrated that AD model mice that received a diet high in the essential nutrient choline had reduced amyloidosis, cholinergic deficits, and gliosis, and increased neurogenesis. In this study, we investigated the lifelong effects of perinatal choline supplementation on behavior, cognitive function, and amyloidosis in AppNL-G-F AD model mice. Pregnant and lactating mice were given a diet containing either 1.1 g/kg (control) or 5 g/kg (supplemented) of choline chloride until weaning and subsequently, all offspring received the control diet throughout their life. At 3, 6, 9, and 12 months of age, animals were behaviorally tested in the Open Field Test, Elevated Plus Maze, Barnes Maze, and in a contextual fear conditioning paradigm. Immunohistochemical analysis of Aβ42 was also conducted on the brains of these mice. AppNL-G-F mice displayed hippocampal-dependent spatial learning deficits starting at 3-months-old that persisted until 12-months-old. These spatial learning deficits were fully prevented by perinatal choline supplementation at young ages (3 and 6 months) but not in older mice (12 months). AppNL-G-F mice also had impaired fearful learning and memory at 9- and 12-months-old that were diminished by choline supplementation. Perinatal choline supplementation reduced Aβ42 deposition in the amygdala, cortex, and hippocampus of AppNL-G-F mice. Together, these results demonstrate that perinatal choline supplementation is capable of preventing cognitive deficits and dampening amyloidosis in AppNL-G-F mice and suggest that ensuring adequate choline consumption during early life may be a valuable method to prevent or reduce AD dementia and neuropathology.

SUBMITTER: Bellio TA

PROVIDER: S-EPMC10843108 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Perinatal choline supplementation prevents learning and memory deficits and reduces brain amyloid Aβ42 deposition in AppNL-G-F Alzheimer's disease model mice.

Bellio Thomas A TA Laguna-Torres Jessenia Y JY Campion Mary S MS Chou Jay J Yee Sheila S Blusztajn Jan K JK Mellott Tiffany J TJ

PloS one 20240205 2

Alzheimer's disease (AD) is characterized by cognitive and memory impairments and neuropathological abnormalities. AD has no cure, inadequate treatment options, and a limited understanding of possible prevention measures. Previous studies have demonstrated that AD model mice that received a diet high in the essential nutrient choline had reduced amyloidosis, cholinergic deficits, and gliosis, and increased neurogenesis. In this study, we investigated the lifelong effects of perinatal choline sup ...[more]

PMID: 38315685

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Project description:Sustainable plant production in soil polluted with heavy metals requires that novel strategies are developed for the benefit of humans and other living things. Cadmium (Cd) is a common heavy metal pollutant for plants, and there is limited information on the use of exogenous bio-regulators to reduce the accumulation and toxic effects of Cd pollution in plants. Choline is an endogenous quertarnary amine that is known to improve stress tolerance in plants, while its mechanism of action in certain conditions is yet to be determined. This study investigated the effects of foliar choline supplementation (10 mM) on Solanum lycopersicum seedlings exposed to Cd application (50 mg/L in soil). The seedlings were randomized to five groups: Control (E1), Cd stress (E2), Choline supplementation after Cd stress (E3), Choline (E4), and Choline supplementation before Cd stress (E5). Following the applications, the Cd content, growth and development parameters (chlorophyll content, fresh and dry weight), oxidative stress parameters (H2O2 and MDA contents), as well as antioxidative defense system (SOD, GSH, AsA, and TPC contents) were analyzed. Choline supplementation after Cd stress reduced the enhanced Cd content in roots by 38% but did not alter it in leaves (p > 0.05) compared to the Cd group. Choline supplementation before Cd stress decreased Cd content both in roots by 87.5% and in leaves by 50%. Choline supplementation after and before Cd stress increased fresh and dry weights in both roots and leaves. While the Cd group (E2) increased the H2O2 level and SOD activity, no remarkable change was observed in H2O2 levels in all choline supplementations (E3, E4, E5). Therefore, lipid peroxidation (MDA) was not observed in choline supplementation before Cd stress (E5), however, when the choline was applied after Cd stress (E3) MDA content was reduced by 40% compared with the Cd stress group (E2). Choline supplementations after and before Cd stress (E3, E5) increased AsA content by 30%, while the Cd group (E2) decreased it by 60% compared with the control group (E1). Choline supplementations before Cd stress (E5) increased TPC by 33%, while the Cd group (E2) decreased it by 18%, moreover, when choline was applied after Cd stress (E3), no change was observed compared to the control group. These data suggest that choline prevents inhibition of plant growth due to Cd toxicity by reducing Cd uptake. The results provided in the present study are likely to enhance the quality and efficiency of crop production in heavy metal-polluted areas.

Dataset Information

Perinatal choline supplementation prevents learning and memory deficits and reduces brain amyloid Aβ42 deposition in AppNL-G-F Alzheimer's disease model mice.

Publications

Perinatal choline supplementation prevents learning and memory deficits and reduces brain amyloid Aβ42 deposition in AppNL-G-F Alzheimer's disease model mice.

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