Department of Clinical Medicine, University in Tromsø-The Arctic University of Norway, 9019 Tromsø, Norway.
University Hospital of North Norway, 9019 Tromsø, Norway.
Learn Mem. 2020 Jan 16;27(2):33-44. doi: 10.1101/lm.050229.119. Print 2020 Feb.
Growth hormone (GH) deficiency is associated with cognitive decline which occur both in normal aging and in endocrine disorders. Several brain areas express receptors for GH although their functional role is unclear. To determine how GH affects the capacity for learning and memory by specific actions in one of the key areas, the hippocampus, we injected recombinant adeno-associated viruses (rAAVs) in male rats to express green fluorescent protein (GFP) combined with either GH, antagonizing GH (aGH), or no hormone, in the dorsal CA1. We found that aGH disrupted memory in the Morris water maze task, and that aGH treated animals needed more training to relearn a novel goal location. In a one-trial spontaneous location recognition test, the GH treated rats had better memory performance for object locations than the two other groups. Histological examinations revealed that GH increased the dendritic spine density on apical dendrites of CA1, while aGH reduced the spine density. GH increased the relative amount of immature spines, while aGH decreased the same amount. Our results imply that GH is a neuromodulator with strong influence over hippocampal plasticity and relational memory by mechanisms involving modulation of dendritic spines. The findings are significant to the increasing aging population and GH deficiency patients.
生长激素（GH）缺乏与认知能力下降有关，这种情况既发生于正常衰老过程中，也发生于内分泌紊乱中。尽管 GH 受体在多个脑区表达，但它们的功能作用尚不清楚。为了确定 GH 通过特定作用对学习和记忆能力的影响，我们在雄性大鼠的背侧 CA1 中注射重组腺相关病毒（rAAV），使其表达绿色荧光蛋白（GFP），同时表达 GH、拮抗 GH（aGH）或不表达任何激素。我们发现，aGH 破坏了 Morris 水迷宫任务中的记忆，并且 aGH 处理的动物需要更多的训练才能重新学习新的目标位置。在单次自发位置识别测试中，GH 处理的大鼠对物体位置的记忆表现优于其他两组。组织学检查显示，GH 增加了 CA1 树突棘的密度，而 aGH 则降低了树突棘密度。GH 增加了不成熟树突棘的相对数量，而 aGH 则减少了相同数量的树突棘。我们的研究结果表明，GH 是一种神经调节剂，通过调节树突棘的机制，对海马体的可塑性和关系记忆具有强烈的影响。这些发现对日益老龄化的人口和 GH 缺乏症患者具有重要意义。
