Objective: To investigate the mechanism of bilirubin-induced neurotoxicity from cellular and molecular level.
Methods: Bilirubin was exposed to primary cultured rat cerebellar granule and cortical neurons and its neurotoxicity was observed DNA staining and agars gel electrophores were used to identify the biochemical and morphological features of bilirubin-induced neurotoxicity in cultured cerebellar granule and cortical neurons.
Results: Bilirubin selectively induced death of cerebellar granule neurons in a concentration- and time-dependent manner. Neuronal death displayed biochemical and morphological features of apoptotic nuclei: condensation of nuclear chromatin and DNA fragmentation. RNA and protein synthesis inhibitors blocked the neurotoxicity induced by bilirubin. However, the cortical neurons displayed a relative insensitivity to bilirubin.
Conclusions: Bilirubin induced neuron death is an active process, requiring de novo synthesis of RNA and protein. Bilirubin may selectively induce apoptosis of cerebellar granule neurons.