title: Experimental epilepsy affects Notch1 signalling and the stem cell pool in the dentate gyrus.
abstract: Temporal lobe epilepsy (TLE) is the most frequent form of epilepsy in adults. In addition to recurrent focal seizures, patients suffer from memory loss and depression. The factors contributing to these symptoms are unknown. In recent years, adult hippocampal neurogenesis has been implicated in certain aspects of learning and memory, as well as in depression and anhedonia. Here we investigated whether the adult hippocampal stem cell niche is affected by status epilepticus in a mouse model of TLE using unilateral intrahippocampal kainic acid injection. Eight days after status epilepticus, we found a strong diminution in Notch signalling, a key pathway involved in stem cell maintenance, as assayed by hes5 reporter gene activity. In particular, hes5-GFP expression in the subgranular zone of the dentate gyrus was diminished. Furthermore, Sox2-positive cells as well as stem cell proliferation were reduced, thus pointing to a disruption of the stem cell niche in epilepsy under the present experimental conditions.
authors.affiliation: Institute of Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany. Mirjam.Sibbe@anat.uni-freiburg.de
authors.forename: Mirjam
authors.initials: M
authors.lastname: Sibbe
authors.forename: Ute
authors.initials: U
authors.lastname: Häussler
authors.forename: Sandra
authors.initials: S
authors.lastname: Dieni
authors.forename: Daniel
authors.initials: D
authors.lastname: Althof
authors.forename: Carola A
authors.initials: CA
authors.lastname: Haas
authors.forename: Michael
authors.initials: M
authors.lastname: Frotscher
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000473:pathology*; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D017930:Genes, Reporter; D007608:Kainic Acid; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051881:Receptor, Notch1 / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D055153:Stem Cell Niche
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D007608:Kainic Acid; D051881:Receptor, Notch1; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; C489685:Hes5 protein, mouse; C497762:Notch1 protein, mouse; C527783:Sox2 protein, mouse