Department for Neurochemistry & Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.
Cell Tissue Res. 2011 Oct;346(1):11-26. doi: 10.1007/s00441-011-1233-3. Epub 2011 Sep 21.
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.
突触电镜蛋白（Bassoon）缺失的小鼠会出现癫痫发作和神经元活动模式改变，伴随着多个脑结构异常增大，其中海马体和皮质的增大最为明显。使用锰增强磁共振成像，发现存在异常脑增大，这种增大在出生后 1 个月首次在海马体中检测到，3 个月后该结构的大小增加近 40%。细胞数量的体视学定量显示，齿状回和海马体的增大与主神经元和星形胶质细胞数量的增加有关。为了寻找潜在的机制，我们发现齿状回中新生细胞的增殖和存活比例增加了约 3 倍，同时齿状回和海马体中双皮质素阳性细胞的数量增加，凋亡细胞的数量减少。海马体和其他前脑结构的增大伴随着脑源性神经营养因子（BDNF）水平的升高。这些数据表明，Bassoon 突变小鼠的海马体过度生长源于神经发生和凋亡的失调，这可能与 BDNF 水平失衡有关。
