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Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Periconceptional folate deficiency leads to autism-like traits in Wistar rat offspring
Stéphanie Degroote1, Darel Hunting2, Larissa Takser1
1Département de Pédiatrie, Faculté de Médecine et Sciences de la Santé, Université de Sherbrooke, Québec, Canada.
Insights
Maternal folate deficiency during pregnancy led to autistic-like behaviors in rat offspring, including reduced social interaction and increased anxiety. This study highlights the critical role of periconceptional one-carbon metabolism in neurodevelopment.
Area of Science:
- Neuroscience
- Developmental Biology
- Nutritional Science
Background:
- Folates are crucial one-carbon donors essential for DNA synthesis and methylation.
- Epidemiological studies suggest a link between folate deficiency and Autism Spectrum Disorders (ASD).
- No prior animal studies have investigated the behavioral effects of periconceptional folate deficiency on autistic phenotypes.
Purpose of the Study:
- To investigate the impact of periconceptional one-carbon metabolism alteration via a folate-deficient diet on rat offspring behavior.
- To determine if maternal folate deficiency during gestation induces an autistic-like phenotype in offspring.
Main Methods:
- Female Wistar rats were fed either a control or a folate-deficient diet (low folic acid, reduced choline, antibiotic) before and during early gestation.
- Offspring underwent a battery of behavioral tests including open field, social interaction, marble burying, elevated plus maze, and prepulse inhibition.
- Blood homocysteine levels were measured to confirm the induced one-carbon donor deficit.
Main Results:
- Offspring exposed to periconceptional folate deficiency exhibited congenital malformations.
- Significant reductions in social sniffing behavior (~30%) and open arm exploration (~50%) were observed, indicating decreased social interaction and increased anxiety.
- Repetitive behaviors, measured by marble burying, increased by ~160%.
- Sensorimotor gating, assessed by prepulse inhibition, was globally impaired by 50%.
Conclusions:
- Maternal periconceptional folate deficiency induces significant behavioral alterations in offspring.
- These behavioral changes are relevant to an autistic-like phenotype.
- The study underscores the importance of maternal nutrition, specifically folate status, for neurodevelopment and behavior in offspring.
Background:
Folates in their role as key one carbon donors, are essential for two major pathways: the synthesis of DNA and RNA precursors and DNA methylation. A growing body of evidence from epidemiological studies indicates a possible association between nutritional and functional deficiency in folates and Autism Spectrum Disorders (ASD). However, there are no available behavioral animal studies on periconceptional one‑carbon donor deficiency during gestation and the autistic phenotype.
Objective:
The objective of this study was to determine if the periconceptional alteration of one‑carbon metabolism induced with a folate deficient diet would affect the behaviour of rat offspring.
Methods:
Female Wistar rats were divided in two groups: control (basal diet, in compliance with standards of regular laboratory diets), or exposed during one month before breeding until Gestational Day 15 to a modified diet with no added folic acid (0.2mg/kg of food), reduced choline (750mg/kg of food), and added 1% SST (a non-absorbable antibiotic used to inhibit folate synthesis by gut bacteria). We administered behavioral tests to offspring, i.e., open field (P20), social interactions (P25), marble burying (P30), elevated plus maze (P35), and prepulse inhibition of the acoustic startle reflex (sensorimotor gating) (P45). Blood homocysteine levels were used to confirm the deficit in one‑carbon donors.
Results:
Compared to controls, offspring with the periconceptional deficit in folate showed: (i) congenital body malformations; (ii) reduced social interactions, with a ~30% decrease in social sniffing behavior; (iii) reduced exploration of the open arm by 50% in the elevated plus maze test, indicating increased anxiety; (iv) a ~160% increased number of marbles buried, indicating repetitive behaviors; and (v) altered sensorimotor gating, with a global 50% decrease in startle inhibition.
Conclusion:
Maternal periconceptional deficit in folate provokes alterations in the behavior of offspring relevant to the autistic-like phenotype.
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