Folate deficiency in rat pups during weaning causes learning and memory deficits

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 237, range 81-484ng/mg protein) and higher homocysteine concentrations (median 277, range 147-455pmol/mg protein), respectively, compared with those of pups on the normal diet (ND; n 9) (median 1145, range 645-1585ng/mg protein and median 155, range 116-189pmol/mg protein) on PND 23. Brain folate concentrations although low were similar in pups on the FD diet (median 105, range 55-245ng/mg protein) and ND (median 111, range 71-242ng/mg protein). There was a high accumulation of homocysteine in the brain of FD pups, mostly in the hippocampus (median 581, range 408-997pmol/mg protein) and cerebellum (median 691, range 508-1266pmol/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 5min, 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.