Impaired neural stem cell expansion and hypersensitivity to epileptic seizures in mice lacking the EGFR in the brain

The FEBS Journal
Jonathan P RobsonMaria Sibilia

Abstract

Mice lacking the epidermal growth factor receptor (EGFR) develop an early postnatal degeneration of the frontal cortex and olfactory bulbs and show increased cortical astrocyte apoptosis. The poor health and early lethality of EGFR-/- mice prevented the analysis of mechanisms responsible for the neurodegeneration and function of the EGFR in the adult brain. Here, we show that postnatal EGFR-deficient neural stem cells are impaired in their self-renewal potential and lack clonal expansion capacity in vitro. Mice lacking the EGFR in the brain (EGFRΔbrain ) show low penetrance of cortical degeneration compared to EGFR-/- mice despite genetic recombination of the conditional allele. Adult EGFRΔ mice establish a proper blood-brain barrier and perform reactive astrogliosis in response to mechanical and infectious brain injury, but are more sensitive to Kainic acid-induced epileptic seizures. EGFR-deficient cortical astrocytes, but not midbrain astrocytes, have reduced expression of glutamate transporters Glt1 and Glast, and show reduced glutamate uptake in vitro, illustrating an excitotoxic mechanism to explain the hypersensitivity to Kainic acid and region-specific neurodegeneration observed in EGFR-deficient brains.

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Citations

Aug 19, 2020·Cells·Roberta Romano, Cecilia Bucci
Apr 1, 2021·The FEBS Journal·Manuel Breuer
Oct 29, 2021·Frontiers in Cell and Developmental Biology·Runzhi HuangJie Zhang
Jan 11, 2022·Developmental Neurobiology·Kang ZhengMengsheng Qiu

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BETA
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transgenic
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