Folic acid ameliorates neonatal isolation-induced autistic like behaviors in rats: epigenetic modifications of BDNF and GFAP promotors
Abstract
The current study investigated the role of epigenetic dysregulation of brain derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) genes and oxidative stress as possible mechanisms of autistic-like behaviors in neonatal isolation model in rats and the impact of folic acid administration on these parameters. Forty Wistar albino pups were used as follows: control, folic acid administered, isolated, and isolated folic acid treated groups. Isolated pups were separated from their mothers for 90 min daily from postnatal day (PND) 1 to 11. Pups (isolated or control) received either the vehicle or folic acid (4 mg/kg/day) orally from PND 1 to 29. Behavioral tests were done from PND 30 to 35. Oxidative stress markers and antioxidant defense in the frontal cortex homogenate were determined. DNA methylation of BDNF and GFAP genes was determined by qPCR. Histopathological examination was carried out. Neonatal isolation produced autistic-like behaviors that were associated with BDNF and GFAP hypomethylation, increased oxidative stress, increased inflammatory cell infiltration, and structural changes in the frontal cortex. Folic acid administration concurrently with isolation reduced neonatal isolation-induced autistic-like behaviors, decreased oxidative stress, regained BDNF and GFAP gene methylation, and ameliorated structural changes in the frontal cortices of isolated folic acid treated rats. Novelty: Neonatal isolation induces “autistic-like” behavior and these behaviors are reversed by folic acid supplementation. Neonatal isolation induces DNA hypomethylation of BDNF and GFAP, increased oxidative stress markers, and neuroinflammation. All of these changes were reversed by daily folic acid supplementation.
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Maternal separation reduces promoter CpG methylation of Gfap in the frontal cortex of adolescent male rats.
“One study found that maternal separation led to reduced promoter CpG methylation of glial fibrillary acidic protein (Gfap), an intermediate filament protein expressed only in astrocytes [137], in the frontal cortex of adolescent male rats [138].”
From Cell-type-specific epigenetic effects of early life stress on the brain (2022) · cites this paper as [138]
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Cell-type-specific epigenetic effects of early life stress on the brain
Rahman, M. F., & McGowan, P. O. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02076-9 · Cited by 75 · see citing works
- Authors
- Ahmed, O. G., Shehata, G. A., Ali, R. M., Makboul, R., Abd Allah, E. S. H., & Abd el-Rady, N. M.
- Affiliations
- Assiut University (EG)
- Medical Physiology Department, Faculty of Medicine, Assiut University, Assiut, Egypt.
- Venue
- Applied Physiology, Nutrition, and Metabolism
- Publisher
- Canadian Science Publishing
- Published
- 2021-08
- Volume
- 46
- Issue
- 8
- Pages
- 964-975
- ISSN
- 1715-5312 (ISSN-L)
- 1715-5320
- OpenAlex
- W3131955855
- Cited by
- 14
- References
- 59
- Citations by year
- 2026: 5 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 1
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Applied Physiology Nutrition and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Keywords
- folic acid, neonatal isolation, autism-like behavior, brain-derived neurotrophic factor, glial fibrillary acidic protein, DNA methylation, epigenetic regulation, oxidative stress, neuroinflammation, frontal cortex, prenatal stress, neuroprotection
- MeSH terms
- Animals, Animals, Newborn, Autistic Disorder, Disease Models, Animal, Folic Acid, Glial Fibrillary Acidic Protein, Vitamin B Complex, Rats, Wistar, Brain-Derived Neurotrophic Factor, Epigenesis, Genetic, Rats
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