Laboratorio de Neurofisiología, Departamento de Biología, Universitat de les Illes Balears, Cra. Valldemossa km 7.5, E-07122 Palma de Mallorca, Spain.
Prog Neuropsychopharmacol Biol Psychiatry. 2013 Aug 1;45:11-20. doi: 10.1016/j.pnpbp.2013.04.005. Epub 2013 Apr 13.
It has been reported that Growth hormone (GH) has an immediate effect enhancing excitatory postsynaptic potentials mediated by AMPA and NMDA receptors in hippocampal area CA1. As GH plays a role in adult memory processing, this work aims to study the acute effects of GH on working memory tasks in rodents and the possible involvement of NMDA and AMPA receptors and also the MEK/ERK signalling pathway. To evaluate memory processes, two different tests were used, the spatial working memory 8-arm radial maze, and the novel object recognition as a form of non-spatial working memory test. Acute GH treatment (1mg/kg i.p., 1h) improved spatial learning in the radial maze respect to the control group either in young rats (reduction of 46% in the performance trial time and 61% in the number of errors), old rats (reduction of 38% in trial time and 48% in the number of errors), and adult mice (reduction of 32% in the performance time and 34% in the number of errors). GH treatment also increased the time spent exploring the novel object respect to the familiar object compared to the control group in young rats (from 63% to 79%), old rats (from 53% to 70%), and adult mice (from 61 to 68%). The improving effects of GH on working memory tests were blocked by the NMDA antagonist MK801 dizocilpine (0.025 mg/kg i.p.) injected 10 min before the administration of GH, in both young and old rats. In addition, the AMPA antagonist DNQX (1mg/kg i.p.) injected 10 min before the administration of GH to young rats, blocked the positive effect of GH. Moreover, in mice, the MEK inhibitor SL 327 (20mg/kg i.p.) injected 30 min before the administration of GH, blocked the positive effect of GH on radial maze and the novel object recognition. In conclusion, GH improved working memory processes through both glutamatergic receptors NMDA and AMPA and it required the activation of extracellular MEK/ERK signalling pathway. These effects could be related to the enhancement of excitatory synaptic transmission in the hippocampus reported by GH.
据报道，生长激素 (GH) 对海马 CA1 区 AMPA 和 NMDA 受体介导的兴奋性突触后电位有即刻作用。由于 GH 在成人记忆处理中发挥作用，本工作旨在研究 GH 对啮齿动物工作记忆任务的急性影响，以及 NMDA 和 AMPA 受体以及 MEK/ERK 信号通路的可能参与。为了评估记忆过程，使用了两种不同的测试，空间工作记忆 8 臂放射迷宫和新颖物体识别作为非空间工作记忆测试的形式。急性 GH 治疗（1mg/kg，ip，1h）改善了空间学习，与对照组相比，年轻大鼠（表现试验时间减少 46%，错误数减少 61%）、老年大鼠（试验时间减少 38%，错误数减少 48%）和成年小鼠（表现时间减少 32%，错误数减少 34%）。GH 治疗还增加了与对照组相比，年轻大鼠（从 63%增加到 79%）、老年大鼠（从 53%增加到 70%）和成年小鼠（从 61%增加到 68%）探索新物体的时间。与对照组相比，年轻和老年大鼠中，NMDA 拮抗剂 MK801 （0.025mg/kg，ip）在 GH 给药前 10 分钟注射，阻断了 GH 对工作记忆测试的改善作用。此外，在年轻大鼠中，在 GH 给药前 10 分钟注射 AMPA 拮抗剂 DNQX（1mg/kg，ip），阻断了 GH 的积极作用。此外，在小鼠中，在 GH 给药前 30 分钟注射 MEK 抑制剂 SL 327（20mg/kg，ip），阻断了 GH 对放射迷宫和新颖物体识别的积极作用。总之，GH 通过 NMDA 和 AMPA 谷氨酸能受体改善工作记忆过程，并且需要细胞外 MEK/ERK 信号通路的激活。这些影响可能与 GH 报道的海马兴奋性突触传递增强有关。
