Pan-ErbB inhibition impairs cognition via disrupting myelination and aerobic glycolysis in oligodendrocytes.

White matter (WM) abnormalities are an emerging feature of schizophrenia, yet the underlying pathophysiological mechanisms are largely unknown. Disruption of ErbB signaling, which is essential for peripheral myelination, has been genetically associated with schizophrenia and WM lesions in schizophrenic patients. However, the roles of ErbB signaling in oligodendrocytes remain elusive.

Sustained ErbB Activation Causes Demyelination and Hypomyelination by Driving Necroptosis of Mature Oligodendrocytes and Apoptosis of Oligodendrocyte Precursor Cells.

Oligodendrocytes are vulnerable to genetic and environmental insults and its injury leads to demyelinating diseases. The roles of ErbB receptors in maintaining the CNS myelin integrity are largely unknown. Here, we overactivate ErbB receptors that mediate signaling of either neuregulin (NRG) or epidermal growth factor (EGF) family growth factors and found their synergistic activation caused deleterious outcomes in white matter.