Enhancement of neural regeneration and neural survival in peripheral nervous system by Novel Liver Derived Neuronal Activator

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Novel liver derived neuronal activator (LDNA) has been proved to enhance neurite regeneration from transected-nerve terminals of adult rat DRG with associated nerve bundles and support their survival. In this project we proved that LDNA promotes neuronal cell survival in adult rat DRG explant after in serum-free culture. After 6 days in culture the explants were rapidly frozen in liquid nitrogen and then sectioned by a cryostat with 10 micron thickness. Nissle bodies in the sections were stained with either Nissle method or Giemsa method. LDNA improved the relative number of Nissle-positive neurons to total neurons from 33% to 40%. These results suggest that LDNA improves neurite regeneration and their survival resulting in inhibition of neuronal cell death. We demonstrated another important function of LDNA that LDNA promotes neuronal regeneration from either vague nerve or > sympathetic nerve both of which contacts with liver. When LDNA was applied to the vagus nerve, this factor enhanced neurite regeneration from the transected-vagus nerve terminals in comparison with that in LDNA-free culture. Similar enhancement by LDNA was seen in neurite regeneration from transected-nerve terminals of superior cervical ganglion. These autonomic nerves are thought to play important roles in either metabolism or regeneration in liver. It is plausible that liver may secrete LDNA and activate either its metabolic function or regeneration capability by promoting autonomic nerve regeneration to contact liver itself.On the other hand we advances the project to determine amino acid sequence of LDNA from 1000 L of hepatocyte conditioned medium. Purification of the factor is going well and it is expected that the amino acid sequence will be determined in an early opportunity. Then we will start to cloning the factor.