Hippocampal enlargement in Bassoon-mutant mice is associated with enhanced neurogenesis, reduced apoptosis, and abnormal BDNF levels

Alexandra Heyden, Mihai Constantin S Ionescu, Stefano Romorini, Bettina Kracht, Veronica Ghiglieri, Paolo Calabresi, Constanze Seidenbecher, Frank Angenstein, Eckart D. Gundelfinger

Research output: Contribution to journalArticlepeer-review

Abstract

Mice mutant for the presynaptic protein Bassoon develop epileptic seizures and an altered pattern of neuronal activity that is accompanied by abnormal enlargement of several brain structures, with the strongest size increase in hippocampus and cortex. Using manganese-enhanced magnetic resonance imaging, an abnormal brain enlargement was found, which is first detected in the hippocampus 1 month after birth and amounts to an almost 40% size increase of this structure after 3 months. Stereological quantification of cell numbers revealed that enlargement of the dentate gyrus and the hippocampus proper is associated with larger numbers of principal neurons and of astrocytes. In search for the underlying mechanisms, an approximately 3-fold higher proportion of proliferation and survival of new-born cells in the dentate gyrus was found to go hand in hand with similarly larger numbers of doublecortin-positive cells and reduced numbers of apoptotic cells in the dentate gyrus and the hippocampus proper. Enlargement of the hippocampus and of other forebrain structures was accompanied by increased levels of brain-derived neurotrophic factor (BDNF). These data show that hippocampal overgrowth in Bassoon-mutant mice arises from a dysregulation of neurogenesis and apoptosis that might be associated with unbalanced BDNF levels.

Original languageEnglish
Pages (from-to)11-26
Number of pages16
JournalCell & Tissue Research
Volume346
Issue number1
DOIs
Publication statusPublished - Oct 2011

Keywords

  • Brain-derived neurotrophic factor
  • Epilepsy
  • Hippocampus
  • Mouse (Bsn mutant)
  • Presynapse

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Histology

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