{Reference Type}: Journal Article
{Title}: HB-EGF activates EGFR to induce reactive neural stem cells in the mouse hippocampus after seizures.
{Author}: Pastor-Alonso O;Durá I;Bernardo-Castro S;Varea E;Muro-García T;Martín-Suárez S;Encinas-Pérez JM;Pineda JR;
{Journal}: Life Sci Alliance
{Volume}: 7
{Issue}: 9
{Year}: 2024 Sep
{Factor}: 5.781
{DOI}: 10.26508/lsa.202201840
{Abstract}: Hippocampal seizures mimicking mesial temporal lobe epilepsy cause a profound disruption of the adult neurogenic niche in mice. Seizures provoke neural stem cells to switch to a reactive phenotype (reactive neural stem cells, React-NSCs) characterized by multibranched hypertrophic morphology, massive activation to enter mitosis, symmetric division, and final differentiation into reactive astrocytes. As a result, neurogenesis is chronically impaired. Here, using a mouse model of mesial temporal lobe epilepsy, we show that the epidermal growth factor receptor (EGFR) signaling pathway is key for the induction of React-NSCs and that its inhibition exerts a beneficial effect on the neurogenic niche. We show that during the initial days after the induction of seizures by a single intrahippocampal injection of kainic acid, a strong release of zinc and heparin-binding epidermal growth factor, both activators of the EGFR signaling pathway in neural stem cells, is produced. Administration of the EGFR inhibitor gefitinib, a chemotherapeutic in clinical phase IV, prevents the induction of React-NSCs and preserves neurogenesis.