INTRAPERITONEAL INJECTION OF FOLINIC ACID (LEUCOVORIN) DID NOT IMPROVE ABNORMALITIES IN BRAIN WEIGHT GROWTH AND BRAIN BIOGENIC AMINE CONCENTRATIONS IN MECP2-NULL MOUSE

Objectives: Empirical treatment with oral folinic acid (leucovorin) was reported to lead partial clinical improvement in some patients with Rett syndrome. We evaluated the efficacy of folinic acid in Rett syndrome model mouse, mecp2-null mouse.

Methods: 1) The brain folate levels of two mecp2-null mice and three male normal littermate mice at postnatal day 42 (P42) were measured by microbiological assay and compared. 2) Folinic acid, 20mg/kg once a day, was injected intraperitoneally from P14 to P42 in three mecp2-null mice and four male normal littermate mice. At P42, mice were anesthetized and whole brains were removed and brain weight and the brain biogenic amine concentration were measured. These data were compared with our previous data of the same strain mice with no treatment.

Results: 1) The brain folate levels of mecp2-null mice were tend to be lower than normal littermate mice (0.53±0.03, 0.85±0.19 nmol/g-tissue, p=0.06). 2) We previously reported that the brain weight and the brain concentrations of norepinephrine, dopamine and serotonine of the mecp2-null mice at P42 were significantlly lowered than that of normal mice. Intraperitoneal injection of folinic acid gave no influence on the differences in brain weight and biogenic amine concentrations between the mecp2-null mice and the normal mice. All three mecp2-null mice with folinic acid injection showed uncoordinated gait and two of three mecp2-null mice showed hindlimb clasping unilaterally at P42.

Conclusion: We found no efficacy of intraperitoneal injection of folinic acid once a day from P14 to P42 in mecp2-null mice. More early treatment may be needed.