Mice with reduced brain-derived neurotrophic factor expression show decreased choline acetyltransferase activity, but regular brain monoamine levels and unaltered emotional behavior
Mice with reduced brain-derived neurotrophic factor expression show decreased choline acetyltransferase activity, but regular brain monoamine levels and unaltered emotional behavior
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DOI：
10.1016/j.molbrainres.2003.11.002
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发表时间：
2004-02-05
期刊：
影响因子：
--
通讯作者：
Gass, P
中科院分区：
文献类型：
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作者：
Chourbaji, S;Hellweg, R;Gass, P
抑郁症的“神经营养素假说”预测，人类抑郁症与脑源性神经营养因子（BDNF）的活性和/或表达降低相一致。因此，我们研究了由于杂合基因破坏导致BDNF表达减少的小鼠是否表现出抑郁样神经化学变化或行为症状。成年BDNF+/-小鼠的BNDF蛋白水平在研究的几个脑区中降低至约60%，包括海马、额叶皮质、纹状体和下丘脑。在这些脑区，单胺（5-羟色胺、去甲肾上腺素和多巴胺）以及5-羟色胺和多巴胺降解产物的含量没有变化。相比之下，在BDNF+/-小鼠的海马中胆碱乙酰转移酶活性显著降低了19%，表明基底前脑的胆碱能系统严重依赖于成年期足够的内源性BDNF水平。此外，BDNF+/-小鼠表现出正常的皮质酮和促肾上腺皮质激素（ACTH）的血清水平在基线条件下和以下制动应力。在一组行为测试中，调查了自发活动，探索，焦虑，恐惧相关的学习和行为绝望，BDNF+/-小鼠与野生型同窝仔没有区别。因此，成年小鼠BDNF蛋白含量的慢性减少不足以诱导神经化学或行为改变，这让人联想到人类的抑郁症状。(C)2003 Elsevier B. V.保留所有权利。
The "neurotrophin hypothesis" of depression predicts that depressive disorders in humans coincide with a decreased activity and/or expression of brain-derived neurotrophic factor (BDNF) in the brain. Therefore, we investigated whether mice with a reduced BDNF expression due to heterozygous gene disruption demonstrate depression-like neurochemical changes or behavioral symptoms. BNDF protein levels of adult BDNF+/- mice were reduced to about 60% in several brain areas investigated, including the hippocampus, frontal cortex, striatum, and hypothalamus. The content of monoamines (serotonin, norepinephrine, and dopamine) as well as of serotonin and dopamine degradation products was unchanged in these brain regions. By contrast, choline acetyltransferase activity was significantly reduced by 19% in the hippocampus of BDNF+/- mice, indicating that the cholinergic system of the basal forebrain is critically dependent on sufficient endogenous BDNF levels in adulthood. Moreover, BDNF+/- mice exhibited normal corticosterone and adrenocorticotropic hormone (ACTH) serum levels under baseline conditions and following immobilization stress. In a panel of behavioral tests investigating locomotor activity, exploration, anxiety, fear-associated learning, and behavioral despair, BDNF+/- mice were indistinguishable from wild-type littermates. Thus, a chronic reduction of BDNF protein content in adult mice is not sufficient to induce neurochemical or behavioral alterations that are reminiscent of depressive symptoms in humans. (C) 2003 Elsevier B.V. All rights reserved.