[Research Articles] Bilirubin enhances the activity of ASIC channels to exacerbate neurotoxicity in neonatal hyperbilirubinemia in mice

In this study, we found that the concentration of the cell death marker, lactate dehydrogenase (LDH) in cerebrospinal fluid (CSF), is elevated in infants with both hyperbilirubinemia and acidosis and showed stronger correlation with the severity of acidosis rather than increased bilirubin concentration. In mouse neonatal neurons, bilirubin exhibits limited toxicity but robustly potentiates the activity of acid-sensing ion channels (ASICs), resulting in increases in intracellular Ca2+ concentration, spike firings, and cell death. Furthermore, neonatal conditioning with concurrent hyperbilirubinemia and hypoxia-induced acidosis promoted long-term impairments in learning and memory and complex sensorimotor functions in vivo, which are largely attenuated in ASIC1a null mice. These findings suggest that targeting acidosis and ASICs may attenuate neonatal hyperbilirubinemia complications.

Source: Science Translational Medicine - February 11, 2020 Category: Biomedical Science Authors: Lai, K., Song, X.-L., Shi, H.-S., Qi, X., Li, C.-Y., Fang, J., Wang, F., Maximyuk, O., Krishtal, O., Xu, T.-L., Li, X.-Y., Ni, K., Li, W.-P., Shi, H.-B., Wang, L.-Y., Yin, S.-K. Tags: Research Articles Source Type: research