Effect of leptin administration on myelination in ob/ob mouse cerebrum after birth

Abstract

Brain weight and size are known to be reduced in adult leptin-deficient Lep/Lep (OB) mice when compared with the wild-type (+/+) mice (C57BL/6: B6). We here analyzed leptin's effects on myelination by examining morphometrically the myelin sheath (MS) in the cerebrum of postnatal day (P) 14 and P28 OB that had received leptin 1 nmol/capita/day from P7 to P14 or P28 (OB+lep), in comparison with OB and B6. We examined myelin basic protein (MBP) mRNA levels and the differentiation of oligodendrocytes by comparing the number of oligodendrocyte precursor cells (OPCs) and the mature oligodendrocytes in the cerebrum between OB, OB+lep, and B6 on P14 and P28. MBP-mRNA expression was lower in OB than in B6 on P14 and P28. On P14, it was higher in OB+lep than in OB but was still lower than in B6, whereas on P28 it was even higher in OB+lep than in B6. On P28, the radii of myelinated axons were larger in OB than in B6 and OB+lep. The MS on P28 was significantly thinner in OB than in B6, but there was no significant difference between OB and OB+lep. There were significantly fewer mature oligodendrocytes in OB and OB+lep than in B6 on P28, whereas on P14 there were significantly fewer OPCs in OB and OB+lep than in B6. Our results suggested that leptin regulates the myelination of oligodendrocytes and that the replenishment of leptin in OB recovered myelination but did not affect the differentiation of OPCs from P7 to P28.