Maternal folic acid modulates neurotrophins and behavior in an animal schizophrenia model

Schizophrenia (SZ) is a complex neuropsychiatric disorder influenced by genetic and environmental factors, including maternal folic acid (FA) deficiency. This study evaluated whether maternal FA supplementation could prevent behavioral and biochemical alterations in offspring exposed to the Poly(I:C)-induced SZ model, a viral RNA analog (2 mg/kg). Female Wistar rats (n = 48) received at doses FA 5 or 10 mg/kg, or vehicle (control), throughout preconception, gestation, and lactation. After lactation, maternal rats underwent locomotor activity and forced swim tests. Adult offspring were subjected to behavioral assessments, including locomotor activity, social interaction, and inhibitory avoidance tests, followed by hippocampal analyses of neurotrophins. The FA 5 mg/kg dose was more effective in preserving memory and social behaviors mainly in the females in the FA5 + Polly group, whereas the 10 mg/kg dose showed less consistent effects. Supplemented groups maintained BDNF, NGF and GDNF levels, indicating a neuroprotective effect against possible immune activation-induced damage, however, FA supplementation failed to preserve NGF levels in males and GDNF levels in females in the FA-supplemented groups. These findings support the neuroprotective role of FA during neurodevelopment, highlighting dose- and sex-dependent variations. Overall, maternal FA supplementation may help prevent SZ-related alterations and inform strategies aimed at promoting maternal and child health and nutrition.