Spatial memory is impaired by peripubertal GnRH agonist treatment and testosterone replacement in sheep.
Spatial memory is impaired by peripubertal GnRH agonist treatment and testosterone replacement in sheep.
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DOI：
10.1016/j.psyneuen.2016.10.016
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发表时间：
2017-01
影响因子：
3.7
通讯作者：
Evans, N. P.
中科院分区：
文献类型：
--
作者：
Hough, D.;Bellingham, M.;Haraldsen, I. R. H.;McLaughlin, M.;Rennie, M.;Robinson, J. E.;Solbakk, A. K.;Evans, N. P.
青春期GnRHa损害长期空间参考记忆。这种GnRHa效应不能被公羊体内的睾丸素替代所抵消。GnRHa对空间定向和学习任务的穿越次数没有影响。在这些空间任务中，GnRHa夸大了情绪反应。睾丸素替代会降低任务中的情绪反应性和积极性。慢性促性腺激素释放激素激动剂(GnRHa)用于治疗，通过下调脑下垂体内GnRH受体来阻断生殖轴内的活动。促性腺激素释放激素受体也在非生殖组织中表达，包括大脑的海马体和杏仁核等区域。长期的GnRHa治疗对海马体依赖的认知功能的影响，如空间定向、学习和记忆，还没有得到很好的研究，特别是当治疗包括青春期等关键的发育窗口时。目前的研究使用了一个绵羊模型来评估在青春期周围时期(8、27和41周)未处理(对照组)、GnRH和睾酮信号均被阻断(GnRHa处理)或GnRH信号特定阻断(GnRHa处理)的公羊的空间迷宫表现和记忆。结果表明，在空间任务中，性腺类固醇信号的阻断降低了情绪反应性，这表现在睾酮替代的恢复作用上，而在空间定向和学习的评估中，穿越时间保持不变。单独阻断GnRH信号与长期空间记忆的保留受损有关，这种影响不能通过睾酮信号的替代而恢复。这些结果表明，GnRH信号可能通过改变空间参照记忆参与空间信息的保持和记忆，而慢性GnRHa治疗可能对这方面的认知功能产生影响。
Peripubertal GnRHa impaired long-term spatial reference memory. This GnRHa-effect was not counteracted with testosterone replacement in rams. Traverse times of spatial orientation and learning tasks were unaffected by GnRHa. GnRHa exaggerated emotional reactivity during these spatial tasks. Testosterone replacement decreased emotional reactivity and motivation in tasks. Chronic gonadotropin-releasing hormone agonist (GnRHa) is used therapeutically to block activity within the reproductive axis through down-regulation of GnRH receptors within the pituitary gland. GnRH receptors are also expressed in non-reproductive tissues, including areas of the brain such as the hippocampus and amygdala. The impact of long-term GnRHa-treatment on hippocampus-dependent cognitive functions, such as spatial orientation, learning and memory, is not well studied, particularly when treatment encompasses a critical window of development such as puberty. The current study used an ovine model to assess spatial maze performance and memory of rams that were untreated (Controls), had both GnRH and testosterone signaling blocked (GnRHa-treated), or specifically had GnRH signaling blocked (GnRHa-treated with testosterone replacement) during the peripubertal period (8, 27 and 41 weeks of age). The results demonstrate that emotional reactivity during spatial tasks was compromised by the blockade of gonadal steroid signaling, as seen by the restorative effects of testosterone replacement, while traverse times remained unchanged during assessment of spatial orientation and learning. The blockade of GnRH signaling alone was associated with impaired retention of long-term spatial memory and this effect was not restored with the replacement of testosterone signaling. These results indicate that GnRH signaling is involved in the retention and recollection of spatial information, potentially via alterations to spatial reference memory, and that therapeutic medical treatments using chronic GnRHa may have effects on this aspect of cognitive function.
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DOI：
10.1016/s0022-4731(85)80011-x
发表时间：
1985-11-01
影响因子：
4.1
作者：
HSUEH, AJW;SCHAEFFER, JM
通讯作者：
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影响因子：
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DOI：
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发表时间：
2010-12
影响因子：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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