Structural determination of sympathetic innervation of mice liver

Abstract

The description of the neural circuitry and brain network involved in the regulation of liver metabolism is of great importance for the understanding of liver physiology and pathophysiology of different metabolic diseases including diabetes and obesity. In the master´s project linked with this present project, it was observed that the chemical sympathectomy of liver induced by neonatal treatment with 6-OHDA abolished the gene expression and the hyperactivity of key enzymes of gluconeogenesis in mice acutely exposed to cold stress, an effect that also observed in liver of rats submmited to hepatic local denervation with phenol. Although these findings suggest that the sympathetic nervous system (SNS) directly activates liver gluconeogenesis. Meanwhile, architecture of sympathetic innervation in liver is still unclear. Thus, in collaboration with Dr. Ana Domingos, at University of Oxford (UK), the goal of the present research plan is to determine the noradrenergic circuitry in mouse liver by 3D reconstruction throught 3DISCO (three-dimensional imaging of solvent-cleared organs) technique, a new anatomical tool that was recently used to describe the sympathetic innervation of white adipose tissue. (AU)