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Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Folate deficiency in rat pups during weaning causes learning and memory deficits
Maria I Berrocal-Zaragoza1, Jeffrey M Sequeira1, Michelle M Murphy2
1Department of Medicine,State University New York (SUNY)-Downstate Medical Center,Box 20, 450 Clarkson Avenue,Brooklyn,NY11203,USA.
Insights
Folate deficiency during weaning in rats impairs brain development, leading to behavioral deficits and cognitive impairments in offspring. Supplementation after weaning did not reverse these negative effects.
Area of Science:
- Neuroscience
- Developmental Biology
- Nutritional Science
Background:
- Folate is crucial for fetal development.
- Gestational folate deficiency is known to cause behavioral deficits in offspring.
- The impact of folate deficiency during the weaning period on brain function requires further investigation.
Purpose of the Study:
- To investigate the effects of folate deficiency during the weaning period on brain function and behavior in rat pups.
- To assess the biochemical markers of folate deficiency in the liver and brain.
- To determine if post-weaning folic acid supplementation can reverse any observed deficits.
Main Methods:
- Rat pups were fed a folate-deficient (FD) diet from postnatal day 1 (PND 1).
- Hepatic and brain folate and homocysteine concentrations were measured on PND 23.
- Behavioral tests assessed developmental deficits, autistic traits (repetitive self-grooming), long-term memory, spatial learning, and set-shifting abilities.
Main Results:
- FD pups exhibited significantly lower hepatic folate and higher homocysteine concentrations compared to normal diet (ND) pups.
- FD pups showed high homocysteine accumulation in the brain, particularly in the hippocampus and cerebellum, indicating metabolic folate deficiency.
- FD pups displayed increased repetitive self-grooming, and deficits in long-term memory, spatial learning, and set-shifting were observed in 12-62% of FD rats, unlike ND rats.
Conclusions:
- Folate deficiency during the weaning period negatively impacts postnatal brain development and function.
- Metabolic folate deficiency in the brain can occur even with normal brain folate concentrations.
- Post-weaning folic acid supplementation is ineffective in correcting these developmental and cognitive deficits.
Abstract:
Folate is essential for fetal development, and its deficiency during gestation causes behavioural deficits in the offspring. The present study investigated its influence during weaning on brain function in the pups of rats that were put on a folate-deficient (FD) diet on postnatal day (PND) 1. Systemic folate deficiency in pups on the FD diet (n 15) was evident from the dramatically lower hepatic folate concentrations (median 23·7, range 8·1-48·4 ng/mg protein) and higher homocysteine concentrations (median 27·7, range 14·7-45·5 pmol/mg protein), respectively, compared with those of pups on the normal diet (ND; n 9) (median 114·5, range 64·5-158·5 ng/mg protein and median 15·5, range 11·6-18·9 pmol/mg protein) on PND 23. Brain folate concentrations although low were similar in pups on the FD diet (median 10·5, range 5·5-24·5 ng/mg protein) and ND (median 11·1, range 7·1-24·2 ng/mg protein). There was a high accumulation of homocysteine in the brain of FD pups, mostly in the hippocampus (median 58·1, range 40·8-99·7 pmol/mg protein) and cerebellum (median 69·1, range 50·8-126·6 pmol/mg protein), indicating metabolic folate deficiency despite normal brain folate concentrations. Developmental deficits or autistic traits were more frequent in the FD group than in the ND group and repetitive self-grooming occurred, on average, three times (range 1-8) v. once (range 0-3) during 5 min, respectively. Long-term memory or spatial learning and set-shifting deficits affected 12 to 62% of rats in the FD group compared with none in the ND group. Post-weaning folic acid supplementation did not correct these deficits. These observations indicate that folate deficiency during weaning affects postnatal development even when gestational folate supply is normal.
