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Modifying Levels of Maternal Dietary Folic Acid or Choline to Study the Impact of Deficiencies on Offspring Health Outcomes
Published on: June 28, 2024
Postnatal choline levels mediate cognitive deficits in a rat model of schizophrenia
Jennifer A Corriveau1, Melissa J Glenn
1Department of Psychology, Colby College, Waterville, ME 04901, USA.
Insights
Choline supplementation protected rats from memory deficits caused by prenatal stress and MK-801, suggesting a protective role for this nutrient in a rat model of schizophrenia.
Area of Science:
- Neuroscience
- Nutritional Psychiatry
- Developmental Psychology
Background:
- Schizophrenia etiology theories suggest early life stress can increase vulnerability to adult challenges, potentially triggering disease onset.
- A rat model was developed to simulate these combined challenges: prenatal stress and adult administration of MK-801, an NMDA antagonist.
- The study aimed to investigate choline's role in mitigating cognitive deficits associated with these modeled schizophrenia-like conditions.
Purpose of the Study:
- To determine if choline protects against schizophrenic-like cognitive deficits in a rat model.
- To examine the impact of choline-supplemented, -deficient, and standard diets on cognitive outcomes.
- To assess how developmental choline levels modulate the effects of prenatal stress and MK-801 exposure.
Main Methods:
- Rats were exposed to prenatal stress or no stress, followed by MK-801 administration in adulthood.
- Choline levels were manipulated via supplemented, deficient, or standard diets from weaning for 25 days.
- Cognitive function was assessed using a novelty preference test for object recognition.
Main Results:
- The model was validated: only rats with both prenatal stress and adult MK-801 showed impaired memory on a standard diet.
- Choline supplementation prevented memory impairment in rats subjected to both prenatal stress and adult MK-801.
- Choline deficiency exacerbated memory deficits in rats exposed to either prenatal stress, MK-801, or both.
Conclusions:
- Developmental choline levels significantly modulate cognitive outcomes in a rat model of schizophrenia.
- Choline supplementation shows potential protective effects against cognitive deficits induced by early-life stress and NMDA receptor antagonism.
- Choline deficiency may increase vulnerability to cognitive impairments resulting from combined prenatal and adult challenges.
Abstract:
In the present study, we investigated whether the essential nutrient choline may protect against schizophrenic-like cognitive deficits in a rat model. Theories regarding the etiology of schizophrenia suggest that early life events render an individual more vulnerable to adult challenges, and the combination may precipitate disease onset. To model this, the adult male offspring of dams who either experienced stress during late gestation or did not were given a 5 mg/kg dose of the NMDA antagonist,MK-801. The presence of both the prenatal challenge of stress and the adult challenge of MK-801 was expected to impair memory in these offspring. Memory was not expected to be impaired in rats that did not experience prenatal stress, but did receive MK-801 as adults. To study whether choline levels altered outcomes in these groups, rats were fed a choline-supplemented, -deficient, or standard diet during the period between the two challenges: beginning at weaning and continuing for 25 days. All rats consumed regular rat chow thereafter. The efficacy of the model was confirmed in the standard fed rats in that only those that were prenatally stressed and received MK-801 as adults displayed impaired memory on a novelty preference test of object recognition. Contrary to this finding and consistent with our hypothesis, choline-supplemented rats that were also both prenatally stressed and given MK-801 as adults showed intact memory. Choline deficiency impaired memory in rats that were just prenatally stressed, just given MK-801 as adults, and subjected to both. Thus, a choline deficient diet may render rats vulnerable to either challenge. Taken together, we offer evidence that developmental choline levels modulate the effects of prenatal stress and/or MK-801 and thereby alter the cognitive outcome in a rat model of schizophrenia.
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