title: Hippocampal enlargement in Bassoon-mutant mice is associated with enhanced neurogenesis, reduced apoptosis, and abnormal BDNF levels.
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.
authors.affiliation: Department for Neurochemistry & Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany. as.heyden@googlemail.com
authors.forename: Alexandra
authors.initials: A
authors.lastname: Heyden
authors.forename: Mihai-Constantin S
authors.initials: MC
authors.lastname: Ionescu
authors.forename: Stefano
authors.initials: S
authors.lastname: Romorini
authors.forename: Bettina
authors.initials: B
authors.lastname: Kracht
authors.forename: Veronica
authors.initials: V
authors.lastname: Ghiglieri
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
authors.forename: Constanze
authors.initials: C
authors.lastname: Seidenbecher
authors.forename: Frank
authors.initials: F
authors.lastname: Angenstein
authors.forename: Eckart D
authors.initials: ED
authors.lastname: Gundelfinger
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001253:Astrocytes / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D018891:Dentate Gyrus / Q000000981:diagnostic imaging / Q000196:embryology*; D000089622:Doublecortin Domain Proteins; D008279:Magnetic Resonance Imaging; D051379:Mice; D008817:Mice, Mutant Strains; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D009929:Organ Size / Q000235:genetics; D011859:Radiography
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C498441:Bsn protein, mouse; D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides