Fig. 9.

Molecular events leading to bilirubin neurodegeneration in a mouse model of neonatal hyperbilirubinemia. a The three sequential phases of the disease progression are indicated: P5, P8 and P10. Representative cartoon showing the morphology of cerebellar sections from WT (black line) and Ugt1 ^-/- (red line). Bilirubin affects cerebellar size of Ugt1 ^-/- mice in a time-dependent manner. Boxes indicate the main pathways and molecular players regulated by bilirubin. b Proposed interplay between the molecular events leading to cerebellar neurodegeneration. Exposure of the developing cerebellum to toxic bilirubin levels triggers the activation of neuroinflammation, ER stress, oxidative stress and autophagy pathways. Bold font indicates main mechanisms involved in the onset of the disease; arrows and molecular markers indicate the interconnection between different mechanisms. An image of a neurodegenerated Purkinje neuron (stained with Calb1, green) surrounded by glial scar (stained with GFAP, red) is represented