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Updated: Jun 8, 2026
Modifying Levels of Maternal Dietary Folic Acid or Choline to Study the Impact of Deficiencies on Offspring Health Outcomes
Published on: June 28, 2024
Effects of postnatal dietary choline manipulation against MK-801 neurotoxicity in pre- and postadolescent rats
1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. Elisabetta.biasi@libero.it
Insights
Postnatal choline supplementation did not protect young rats from NMDA antagonist neurotoxicity. However, low choline levels appeared to suppress piriform cortex neurotoxicity in immature female rats after 60 days.
Area of Science:
- Neuroscience
- Developmental Biology
- Nutritional Science
Background:
- Prenatal choline supplementation offers neuroprotection against NMDA antagonist toxicity.
- The effects of postnatal choline exposure on neuroprotection remain less understood.
Purpose of the Study:
- To investigate if postnatal dietary choline supplementation or deprivation in young rats induces neuroprotection against NMDA antagonist-induced neurotoxicity.
- To examine the impact of choline levels on neuronal degeneration in specific brain regions.
Main Methods:
- Male and female Sprague-Dawley rats (postnatal day 30) were fed diets varying in choline levels (deficient to 7x normal) for 30 or 60 days.
- Rats received an injection of MK-801 (an NMDA antagonist) or saline control.
- Brain histology with Fluorojade-C staining was used to assess neuronal degeneration in the retrosplenial and piriform cortices.
Main Results:
- MK-801 induced significant neuronal degeneration, confirmed by Fluorojade-C staining.
- Postnatal choline manipulation did not alter NMDA antagonist-induced neurodegeneration in the retrosplenial cortex.
- Neurotoxicity was absent in the hippocampus and dentate gyrus; piriform cortex was unaffected in young males.
- Low dietary choline levels suppressed piriform cortex neurotoxicity in immature females after 60 days of exposure.
Conclusions:
- Postnatal choline exposure alone does not confer neuroprotection against NMDA antagonist toxicity in young rats.
- Sex-specific differences in neurotoxicity susceptibility and choline's protective effects were observed.
- Dietary choline levels during development may influence vulnerability to specific neurotoxic insults in a region- and sex-dependent manner.
Abstract:
Prenatal supplementation of rat dams with dietary choline has been shown to provide their offspring with neuroprotection against N-methyl-d-aspartate (NMDA) antagonist-mediated neurotoxicity. This study investigated whether postnatal dietary choline supplementation exposure for 30 and 60 days of rats starting in a pre-puberty age would also induce neuroprotection (without prenatal exposure). Male and female Sprague-Dawley rats (postnatal day 30 of age) were reared for 30 or 60 concurrent days on one of the four dietary levels of choline: 1) fully deficient choline, 2) 1/3 the normal level, 3) the normal level, or 4) seven times the normal level. After diet treatment, the rats received one injection of MK-801 (dizocilpine 3mg/kg) or saline control. Seventy-two hours later, the rats were anesthetized and transcardially perfused. Their brains were then postfixed for histology with Fluorojade-C (FJ-C) staining. Serial coronal sections were prepared from a rostrocaudal direction from 1.80 to 4.2mm posterior to the bregma to examine cell degeneration in the retrosplenial and piriform regions. MK-801, but not control saline, produced significant numbers of FJ-C positive neurons, indicating considerable neuronal degeneration. Dietary choline supplementation or deprivation in young animals reared for 30-60days did not alter NMDA antagonist-induced neurodegeneration in the retrosplenial region. An interesting finding is the absence of the piriform cortex involvement in young male rats and the complete absence of neurotoxicity in both hippocampus regions and DG. However, neurotoxicity in the piriform cortex of immature females treated for 60days appeared to be suppressed by low levels of dietary choline.
