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 autisticlike
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 stressmarkers, and neuroinflammation.
All of these changes were reversed by daily folic acid supplementation.
Key words: autistic like behaviors, BDNF, folate, GFAP, methylation.