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Use of a Piglet Model for the Study of Anesthetic-induced Developmental Neurotoxicity (AIDN): A Translational Neuroscience Approach
Published on: June 11, 2017
Developmental sensitivity of the piglet brain to docosahexanoic acid
S A Morris1, K N Simmer, van Barneveld R
1Faculty of Health Sciences, Flinders University of South Australia, Bedford Park, Australia.
Insights
Human infants fed formula have lower docosahexaenoic acid (DHA) levels in the brain. Piglet studies suggest DHA supplementation can reverse this deficit, even later in infancy, indicating potential for catch-up growth.
Area of Science:
- Neuroscience
- Nutritional Science
- Developmental Biology
Background:
- Human formula-fed infants exhibit lower cerebral cortex docosahexaenoic acid (DHA) concentrations compared to breast-fed infants.
- The reversibility of this DHA deficit in later infancy remains uncertain.
Purpose of the Study:
- To investigate the existence of a critical window for docosahexaenoic acid (DHA) deposition in the cerebral cortex during early postnatal development using a piglet model.
- To determine if DHA supplementation can reverse lower DHA levels in infant brains.
Main Methods:
- Piglets were fed DHA-supplemented milk formula during either an early (starting at 2 days) or late (starting at 16 days) 14-day period.
- Cortical DHA levels were compared between supplemented piglets and age-matched controls receiving DHA-devoid formula.
- Whole brain and cerebral cortex DHA levels were analyzed, considering the impact of myelination.
Main Results:
- Dietary DHA was efficiently incorporated into the cerebral cortex during both early and late supplementation periods in piglets.
- Analysis of whole brain DHA was misleading; cerebral cortex analysis revealed DHA responsiveness.
- Piglet plasma and liver phospholipid DHA levels increased significantly during control formula feeding, suggesting higher endogenous DHA synthesis compared to humans.
Conclusions:
- The piglet cerebral cortex demonstrates responsiveness to dietary DHA during the postnatal brain growth spurt.
- Lower cortical DHA levels observed in human formula-fed infants may be reversible in later infancy.
- The piglet model has limitations due to potentially higher endogenous DHA synthesis rates compared to human infants.
Abstract:
Human formula-fed infants have a lower concentration of docosahexanoic acid (DHA) in cerebral cortex compared with breast-fed infants. It is uncertain whether this biochemical deficit is reversible in later infancy. We used a piglet model to determine whether a critical window exists for the deposition of DHA in cerebral cortex during early postnatal development. Milk formula supplemented with DHA was fed to piglets for one of two 14-day periods commencing at either 2 or 16 d of life (early or late supplementation). Comparison of cortical DHA levels in response to supplemented formula was made with age-matched piglets receiving a control formula devoid of DHA. The level of DHA incorporated into whole brain during supplemented formula-feeding seemed to be less with increasing postnatal age. However, when cerebral cortex was examined, dietary DHA was efficiently incorporated during both early and late supplementation periods. Thus, analysis of whole brain was misleading, emphasizing the need to consider the effect of myelination when interpreting developmental changes in brain fatty acids. We conclude that the piglet cerebral cortex is responsive to dietary DHA during the postnatal phase of the brain growth spurt. The lower cortical DHA levels of human formula-fed infants may, therefore, be reversible in later infancy. Plasma phospholipid DHA levels were approximately doubled and liver phospholipid DHA levels increased 50% relative to starting values during control formula-feeding. This suggests a higher rate of DHA synthesis in the piglet in comparison with the human infant, which may be an important limitation of the piglet model.

