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Impaired neural stem cell expansion and hypersensitivity to epileptic seizures in mice lacking the EGFR in the brain
Author(s) -
Robson Jonathan P.,
Wagner Bettina,
Glitzner Elisabeth,
Heppner Frank L.,
Steinkellner Thomas,
Khan Deeba,
Petritsch Claudia,
Pollak Daniela D.,
Sitte Harald H.,
Sibilia Maria
Publication year - 2018
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14603
Subject(s) - astrogliosis , neurodegeneration , neuroscience , astrocyte , glutamate receptor , kainic acid , neural stem cell , biology , glutamatergic , medicine , pathology , central nervous system , stem cell , receptor , microbiology and biotechnology , genetics , disease
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 (EGFR Δbrain ) show low penetrance of cortical degeneration compared to EGFR −/− mice despite genetic recombination of the conditional allele. Adult EGFR Δ 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.