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Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Perinatal Brain Docosahexaenoic Acid Concentration Has a Lasting Impact on Cognition in Mice
Luis E Lozada1,2, Abhishek Desai2, Karl Kevala2
1Department of Pediatrics, Walter Reed National Military Medical Center, Bethesda, MD; and.
Insights
Early omega-3 fatty acid (ω-3 FA) supplementation is crucial for correcting cognitive deficits in infant mice deprived of docosahexaenoic acid (DHA). Supplementation after 3 weeks of age did not fully restore learning and memory functions.
Area of Science:
- Neuroscience
- Developmental Biology
- Nutritional Science
Background:
- Premature infants miss crucial prenatal docosahexaenoic acid (DHA) accumulation, vital for cognitive development.
- Dietary omega-3 fatty acid (ω-3 FA) deficiency in early life impacts brain development.
- ω-3 FA supplementation can reverse brain DHA deficits.
Purpose of the Study:
- To determine if a critical developmental window exists for ω-3 FA supplementation to correct cognitive deficits.
- To investigate the long-term effects of developmental ω-3 FA deprivation and subsequent supplementation on cognitive function in mice.
Main Methods:
- Timed-pregnant mice were fed ω-3 FA-deficient or adequate diets.
- Offspring were maintained on deficient diets or switched to adequate diets at specific ages (3 weeks, 2 months, 4 months).
- Cognitive function, learning, memory, and hippocampal synaptic protein expression were assessed at 6 months.
Main Results:
- Developmental ω-3 FA deprivation significantly reduced brain DHA levels and impaired learning and memory.
- Synaptic protein expression in the hippocampus was reduced in deprived mice.
- Dietary correction of DHA levels was effective at all ages, but cognitive and synaptic function recovery was only observed when supplemented by 3 weeks of age.
Conclusions:
- Early-life developmental deprivation of DHA has lasting negative impacts on cognitive function.
- There is a critical developmental period for ω-3 FA supplementation to normalize cognitive deficits.
- Timely intervention is essential to prevent long-term cognitive impairments.
Abstract:
Background: Premature infants are deprived of prenatal accumulation of brain docosahexaenoic acid [DHA (22:6n-3)], an omega-3 fatty acid [ω-3 FA (n-3 FA)] important for proper development of cognitive function. The resulting brain DHA deficit can be reversed by ω-3 FA supplementation.Objective: The objective was to test whether there is a critical period for providing ω-3 FA to correct cognitive deficits caused by developmental ω-3 FA deprivation in mice.Methods: Twelve timed-pregnant mice [embryonic day 14 (E14), C57/BL6NCr] were fed an ω-3 FA-deficient diet containing 0.04% α-linolenic acid [ALA (18:3n-3)], and their offspring were fed the same deficient diet (Def group) or changed to an ω-3 FA-adequate diet containing 3.1% ALA at 3 wk, 2 mo, or 4 mo of age. In parallel, 3 E14 pregnant mice were fed the adequate diet and their offspring were fed the same diet (Adeq group) throughout the experiment. Brain FA composition, learning and memory, and hippocampal synaptic protein expression were evaluated at 6 mo by gas chromatography, the Morris water maze test, and western blot analysis, respectively.Results: Maternal dietary ω-3 FA deprivation decreased DHA by >50% in the brain of their offspring at 3 wk of age. The Def group showed significantly worse learning and memory at 6 mo than those groups fed the adequate diet. These pups also had decreased hippocampal expression of postsynaptic density protein 95 (43% of Adeq group), Homer protein homolog 1 (21% of Adeq group), and synaptosome-associated protein of 25 kDa (64% of Adeq group). Changing mice to the adequate diet at 3 wk, 2 mo, or 4 mo of age restored brain DHA to the age-matched adequate concentration. However, deficits in hippocampal synaptic protein expression and spatial learning and memory were normalized only when the diet was changed at 3 wk.Conclusion: Developmental deprivation of brain DHA by dietary ω-3 FA depletion in mice may have a lasting impact on cognitive function if not corrected at an early age.
