Reduced hippocampal neurogenesis in the GR(+/-) genetic mouse model of depression.
Reduced hippocampal neurogenesis in the GR(+/-) genetic mouse model of depression.
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DOI：
10.1007/s00406-009-0036-y
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发表时间：
2009-12
影响因子：
4.7
通讯作者：
Gass P
中科院分区：
文献类型：
--
作者：
Kronenberg G;Kirste I;Inta D;Chourbaji S;Heuser I;Endres M;Gass P
糖皮质激素受体（GR）杂合子小鼠（GR+/−）是一种有价值的抑郁症动物模型。GR+/−小鼠表现出抑郁症相关表型，其特征在于行为水平上的习得性无助增加以及具有抑郁症特征的下丘脑-垂体-肾上腺（HPA）轴的神经内分泌改变。海马脑源性神经营养因子（BDNF）水平也被证明在GR+/−动物中降低。由于成人海马神经发生与情感障碍的病理生理学有关，我们在此研究了GR+/−基因型对体内神经发生的影响。在2 × 2设计中，GR+/−小鼠和GR+/+同窝对照小鼠在腹膜内注射BrdU后，要么接受1小时的束缚应激，要么在其饲养笼中不受干扰。每天进行一次应激暴露和BrdU注射，持续7天，4周后分析神经发生。BrdU细胞计数显着减少GR+/−基因型的影响，并作为压力的影响。大多数BrdU+细胞显示与成熟神经元标记物NeuN或星形胶质细胞标记物S100β共标记，实验条件或基因型均无进一步显著影响。总之，这导致GR+/−小鼠的神经发生减少，这进一步受到束缚应激的抑制。因此，我们的研究结果加强了神经发生减少、压力、神经营养因子和抑郁症的行为症状和易感性之间的联系。
Glucocorticoid receptor (GR) heterozygous mice (GR+/−) represent a valuable animal model for major depression. GR+/− mice show a depression-related phenotype characterized by increased learned helplessness on the behavioral level and neuroendocrine alterations with hypothalamo-pituitary-adrenal (HPA) axis overdrive characteristic of depression. Hippocampal brain-derived neurotrophic factor (BDNF) levels have also been shown to be reduced in GR+/− animals. Because adult hippocampal neurogenesis has been implicated in the pathophysiology of affective disorders, we studied here the effects of the GR+/− genotype on neurogenesis in vivo. In a 2 × 2 design, GR+/− mice and GR+/+ littermate controls were either subjected to 1 h of restraint stress or left undisturbed in their home cages after intraperitoneal injection of BrdU. Stress exposure and BrdU injections were performed once daily for 7 days and neurogenesis analyzed 4 weeks later. BrdU cell counts were significantly reduced as an effect of GR+/− genotype and as an effect of stress. Majority of the BrdU+ cells showed co-labeling with mature neuronal marker NeuN or astrocytic marker S100β with no further significant effect of either experimental condition or of genotype. In sum, this results in reduced neurogenesis in GR+/− mice which is further repressed by restraint stress. Our results, thus, reinforce the link between reduced neurogenesis, stress, neurotrophins, and behavioral symptoms of and susceptibility to depression.
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影响因子：
56.9
作者：
Santarelli, L;Saxe, M;Hen, R
通讯作者：
Hen, R
影响因子：
2.5
作者：
Kronenberg, G;Reuter, K;Kempermann, G
通讯作者：
Kempermann, G
影响因子：
16.2
作者：
Pollak, Daniela D.;Monje, Francisco J.;Kandell, Eric R.
通讯作者：
Kandell, Eric R.
影响因子：
10.6
作者：
Czéh, B;Welt, T;Keck, ME
通讯作者：
Keck, ME
DOI：
10.1073/pnas.95.6.3168
发表时间：
1998-03-17
影响因子：
11.1
作者：
Gould, E;Tanapat, P;Fuchs, E
通讯作者：
Fuchs, E