Grosse Gisela, Djalali Susann, Deng Dong Rui, Höltje Markus, Hinz Britta, Schwartzkopff Katharina, Cygon Marcel, Rothe Thomas, Stroh Thomas, Hellweg Rainer, Ahnert-Hilger Gudrun, Hörtnag Heide
Centre for Anatomy, Functional Cell Biology, Charité-Medical Faculty, Free University and Humboldt University, D-10115 Berlin, Germany.
Brain Res Dev Brain Res. 2005 May 12;156(2):111-26. doi: 10.1016/j.devbrainres.2004.12.012.
The effects of brain-derived neurotrophic factor (BDNF) on the development of presynaptic terminals and of neuronal subtypes in various brain areas were studied in BDNF-knockout (BDNF-/-) mice at postnatal days 15-17. Western analysis revealed no changes in the overall amount of a variety of synaptic proteins in BDNF-/- mice as compared to wild type mice. In addition, the complex between the vesicular proteins, synaptophysin and synaptobrevin, as well as their respective homodimers were unaltered. Moreover, no changes in the density of neurons were found in, e.g., the CA3 region of the hippocampus and the nucleus nervi facialis of BDNF-/- mice. However, cholinergic cells were reduced by 20% in the medial septum of BDNF-/- mice associated with a decrease in the activity of choline acetyltransferase and protein levels of nerve growth factor in the hippocampus by 16% and 44%, respectively. In the striatum, however, the total number of cholinergic cells were comparable in both groups, although the activity of choline acetyltransferase was decreased by 46%. In GABAergic interneurons, the expression of neuropeptides in various brain areas was differentially affected by BDNF deletion as revealed by immunohistochemistry. In the hippocampus and cortex of BDNF-/- mice, the density of neuropeptide Y-, somatostatin-, and parvalbumin-immunoreactive cells was drastically reduced, whereas the density of calretinin-positive cells was increased. The extent of these changes in neuropeptide-containing cells varied among hippocampal subregions. In the striatum, only the density of parvalbumin-immunoreactive cells was decreased by approximately 45%. In conclusion, BDNF deficiency is accompanied by a differential dysregulation in the expression of neuropeptides and calcium-binding proteins in otherwise intact GABAergic and glutamatergic neurons in a region-specific manner.
在出生后第15 - 17天的脑源性神经营养因子（BDNF）基因敲除（BDNF-/-）小鼠中，研究了BDNF对不同脑区突触前终末和神经元亚型发育的影响。蛋白质免疫印迹分析显示，与野生型小鼠相比，BDNF-/-小鼠中多种突触蛋白的总量没有变化。此外，囊泡蛋白、突触小泡蛋白和突触融合蛋白之间的复合物及其各自的同型二聚体也未改变。而且，在BDNF-/-小鼠的海马CA3区和面神经核等区域，未发现神经元密度有变化。然而，BDNF-/-小鼠内侧隔区的胆碱能细胞减少了20%，同时海马中胆碱乙酰转移酶的活性和神经生长因子的蛋白水平分别降低了16%和44%。然而，在纹状体中，两组胆碱能细胞的总数相当，尽管胆碱乙酰转移酶的活性降低了46%。免疫组织化学结果显示，在GABA能中间神经元中，BDNF缺失对不同脑区神经肽的表达有不同影响。在BDNF-/-小鼠的海马和皮质中，神经肽Y、生长抑素和小白蛋白免疫反应性细胞的密度大幅降低，而钙视网膜蛋白阳性细胞的密度增加。这些含神经肽细胞的变化程度在海马亚区之间有所不同。在纹状体中，只有小白蛋白免疫反应性细胞的密度降低了约45%。总之，BDNF缺乏伴随着在区域特异性方式下，原本完整的GABA能和谷氨酸能神经元中神经肽和钙结合蛋白表达的差异性失调。
