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

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 imag...

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Bibliographic Details
Published in:Cell and tissue research 2011-10, Vol.346 (1), p.11-26
Main Authors: Heyden, Alexandra, Ionescu, Mihai-Constantin S, Romorini, Stefano, Kracht, Bettina, Ghiglieri, Veronica, Calabresi, Paolo, Seidenbecher, Constanze, Angenstein, Frank, Gundelfinger, Eckart D
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Apoptosis - physiology
astrocytes
Astrocytes - metabolism
Biomedical and Life Sciences
Biomedicine
Brain
Brain-derived neurotrophic factor
Brain-Derived Neurotrophic Factor - metabolism
Cell Proliferation
Cell Survival - physiology
cortex
Dentate Gyrus - diagnostic imaging
Dentate Gyrus - embryology
Developmental biology
Epilepsy
hippocampus
Human Genetics
Indexing in process
Magnetic Resonance Imaging
Mice
Mice, Mutant Strains
Microtubule-Associated Proteins - genetics
Microtubule-Associated Proteins - metabolism
Molecular Medicine
mutants
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
neurogenesis
Neurogenesis - physiology
Neurons
Neurons - metabolism
Neuropeptides - genetics
Neuropeptides - metabolism
Organ Size - genetics
Proteomics
Radiography
Regular Article
Rodents
seizures
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Summary: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.
ISSN:0302-766X
1432-0878
DOI:10.1007/s00441-011-1233-3