Adrenalectomy-induced granule cell degeneration in the hippocampus causes spatial memory deficits that are not reversed by chronic treatment with corticosterone or fluoxetine.
Adrenalectomy-induced granule cell degeneration in the hippocampus causes spatial memory deficits that are not reversed by chronic treatment with corticosterone or fluoxetine.
复制标题
肾上腺切除术引起的海马颗粒细胞变性会导致空间记忆缺陷，而长期使用皮质酮或氟西汀治疗无法逆转这种缺陷。
DOI：
10.1002/hipo.20252
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发表时间：
2007
期刊：
影响因子：
3.5
通讯作者：
Sutherland,RobertJ
中科院分区：
文献类型：
--
作者：
Spanswick,SimonC;Epp,JonathanR;Keith,JulianR;Sutherland,RobertJ
长期肾上腺切除术（ADX）导致海马齿状回（DG）中颗粒细胞几乎完全和选择性丧失。以前，在ADX诱导的颗粒细胞变性后，已经观察到学习和记忆缺陷，这些任务需要海马体。我们的目的是确定皮质酮（CORT）替代和神经源性化合物氟西汀治疗是否可以逆转ADX后的行为缺陷。在CORT和氟西汀或溶媒长期给药（6周）之前，我们在移动的隐藏平台版本的Morris水任务中训练ADX和对照大鼠。治疗后，所有大鼠在Morris水任务中重新测试。用内源性神经源性标记物Ki 67和doublecortin标记大脑。在这里，我们提供的证据表明，在长期ADX后，海马体中的神经发生以正常速率持续存在。CORT和氟西汀给药8周后，ADX-氟西汀大鼠与接受CORT的ADX-溶媒大鼠或对照大鼠相比，Ki 67或双皮质素标记细胞的数量无显著差异。在颗粒细胞层厚度方面，ADX-氟西汀大鼠与ADX-溶剂组大鼠也无显著差异。我们的研究结果表明，长期ADX与Morris水任务中的空间能力受损相关，并且无论是CORT长期治疗，还是CORT和氟西汀都不能改变Morris水任务缺陷。© 2006 Wiley利斯公司
Long‐term adrenalectomy (ADX) causes a nearly complete and selective loss of granule cells in the dentate gyrus (DG) of the hippocampus. Previously, learning and memory deficits have been observed following ADX‐induced granule cell degeneration for tasks that require the hippocampus. Our objective here was to determine whether corticosterone (CORT) replacement and treatment with the neurogenic compound fluoxetine could reverse behavioral deficits after ADX. We trained ADX and control rats in a moving, hidden platform version of the Morris water task before chronic administration (6 weeks) of CORT and either fluoxetine or vehicle. After treatment, all rats were retested in the Morris water task. Brains were labeled for the endogenous neurogenic markers Ki67 and doublecortin. Here we provide evidence that neurogenesis persists at a normal rate in the hippocampus after long‐term ADX. After 8 weeks of CORT and fluoxetine administration, ADX‐fluoxetine rats did not differ significantly compared to ADX‐vehicle rats receiving CORT or compared to control rats in the number of Ki67 or doublecortin labeled cells. ADX‐fluoxetine rats also did not significantly differ from ADX‐vehicle rats in regards to granule cell layer thickness. Our results indicate that long‐term ADX is associated with impaired spatial ability in the Morris water task and that neither chronic treatment with CORT, nor with CORT and fluoxetine are capable of altering the Morris water task deficit. © 2006 Wiley‐Liss, Inc.