Direct and indirect effects of neuropeptide Y and neurotrophin 3 on myelination in the neonatal brains

Neuropeptide Y (NPY) is expressed in the developing central nervous system, however, its role in the brain development remains unclear. In this study, C57/B6 mice were intraperitoneally administered 1 nmol/capita/day of NPY, 10 nmol/capita/day of an NPY-receptor 1-specific antagonist (Y1R-A), or NPY and Y1R-A simultaneously (NPY+Y1R-A) from postnatal day (P) 7 to P14. Recombinant NPY reached the P14 cerebrum in 1 hour. These treatments didn't significantly affect body weight gain or P14 brain weight. The ratio of myelinated axons to total axons in the parietal cerebrum was significantly higher in the NPY group than in the control group. The expression of myelin basic protein (MBP)-mRNA in the cerebrum was significantly higher in the NPY group than in the control group and was significantly lower in the NPY+Y1R-A group than in the NPY group, while it was significantly higher in the NPY+Y1R-A group than in the control group. In cultured oligodendroglioma-derived B12 cells, NPY didn't influence the MBP-mRNA expression, while neurotrophin 3 (NT3) increased MBP mRNA via receptor-type tyrosine kinase type C (Trk C). NPY administration significantly increased NT3-mRNA expression in the P14 cerebrum as deduced by quantitative real-time PCR. The change in phosphorylated Trk C (P-Trk C) was proportional to that of the NT3-mRNA expression, and the proportion of P-Trk C was higher in the NPY group than in the control group. These results suggest that NPY, partially via Y1R, induces NT3 which, via Trk C phosphorylation, accelerates myelination by oligodendrocytes in the mouse brain during the neonatal period. (c) 2010 Elsevier B.V. All rights reserved.