DENTATE GYRUS DESTRUCTION AND SPATIAL-LEARNING IMPAIRMENT AFTER CORTICOSTEROID REMOVAL IN YOUNG AND MIDDLE-AGED RATS

DENTATE GYRUS DESTRUCTION AND SPATIAL-LEARNING IMPAIRMENT AFTER CORTICOSTEROID REMOVAL IN YOUNG AND MIDDLE-AGED RATS
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DOI:
10.1002/hipo.450050103
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发表时间:
1995-01-01
期刊:
影响因子:
3.5
通讯作者:
ROY, EJ
ROY, EJ
中科院分区:
医学3区
文献类型:
--
作者:
CONRAD, CD;ROY, EJ

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我们研究了长期去除皮质类固醇对年轻和中年大鼠的功能和行为影响。青春期前和 13 个月大的大鼠被切除肾上腺 (ADX) 或假手术 (SHAM)。年轻的 ADX 大鼠进一步分为三组:不进行激素替代的 ADX、长期给予皮质酮的 ADX (chCORT) 和在 Morris 水迷宫测试时急性给予皮质酮的 ADX (acCORT)。手术后 12 周,所有大鼠均在 Morris 水迷宫中进行实验。然后将它们处死并取出大脑进行组织学分析。结果表明,长期缺乏皮质类固醇会对齿状回造成严重损害,并导致莫里斯水迷宫的学习障碍。 chCORT 大鼠几乎没有齿状回细胞损失,并且在 Morris 水迷宫表现方面与对照组一样有效,而 acCORT 大鼠则有齿状回细胞损失,并且在空间获取任务中受损。此外,外源性给予皮质酮对 ADX 大鼠具有交互作用。与未给予皮质酮的 ADX 大鼠相比,齿状回损伤大鼠 (acCORT) 的水迷宫表现有所改善,而齿状回损伤极少的 ADX 大鼠 (chCORT) 相对于对照组并未表现出更好的水迷宫表现。中年 ADX 大鼠仅在齿状回背叶中丢失细胞,但与中年对照组相比,它们在莫里斯水迷宫中并未表现出学习障碍。这些结果表明,皮质类固醇对齿状回有营养作用,成熟的颗粒细胞受肾上腺切除术的影响较小,皮质类固醇的缺乏是 ADX 大鼠中某些水迷宫损伤的原因,但除了皮质类固醇的缺乏之外,大量的齿状回损伤也是损害空间学习所必需的。 (C) 1995 Wiley-Liss, Inc.
We investigated the functional and behavioral implications of chronic corticosteroid removal in young and middle-aged rats. Prepubertal and 13-month-old rats were adrenalectomized (ADX) or sham operated (SHAM). The young ADX rats were divided further into three groups: ADX with no hormone replacement, ADX given corticosterone chronically, (chCORT), and ADX given corticosterone acutely at the time of Morris water maze testing (acCORT). All rats were run on the Morris water maze 12 weeks after surgery. They were then sacrificed and the brains were removed for histological analysis.The results showed that prolonged corticosteroid absence caused major damage to the dentate gyrus and learning impairment on the Morris water maze. The chCORT rats had little dentate gyrus cell loss and were as efficient as the controls in Morris water maze performance, whereas the acCORT rats had dentate gyrus cell loss and were impaired in the spatial acquisition task. Furthermore, exogenously administered corticosterone had an interactive effect on ADX rats. Water maze performance was improved in dentate gyrus damaged rats (acCORT) compared to ADX rats not given corticosterone, whereas ADX rats with very little dentate gyrus damage (chCORT) did not exhibit better water maze performance relative to controls. Middle-aged ADX rats lost cells only in the dorsal blade of the dentate gyrus but they did not show a learning impairment in the Morris water maze relative to the middle-aged controls. These results indicate that corticosteroids are trophic for the dentate gyrus, that mature granule cells are less affected by adrenalectomy, that corticosteroid absence is responsible for some water maze impairment in ADX rats, but that in addition to corticosteroid absence, a substantial amount of dentate gyrus damage is necessary to impair spatial learning. (C) 1995 Wiley-Liss, Inc.