%0 Journal Article
%T HB-EGF activates EGFR to induce reactive neural stem cells in the mouse hippocampus after seizures.
%A Pastor-Alonso O
%A Durá I
%A Bernardo-Castro S
%A Varea E
%A Muro-García T
%A Martín-Suárez S
%A Encinas-Pérez JM
%A Pineda JR
%J Life Sci Alliance
%V 7
%N 9
%D 2024 Sep
%M 38977310
%F 5.781
%R 10.26508/lsa.202201840
%X 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.