Spaceflight and simulated microgravity both affect learning and memory, which are mostly controlled by the hippocampus. However, data about molecular alterations in the hippocampus in real or simulated microgravity conditions are limited. Adult Wistar rats were recruited in the experiments. Here we analyzed whether short-term simulated microgravity caused by 3-day hindlimb unloading (HU) will affect the glutamatergic and GABAergic systems of the hippocampus and how dynamic foot stimulation (DFS) to the plantar surface applied during HU can contribute in the regulation of hippocampus functioning. The results demonstrated a decreased expression of vesicular glutamate transporters 1 and 2 (VGLUT1/2) in the hippocampus after 3 days of HU, while glutamate decarboxylase 67 (GAD67) expression was not affected. HU also significantly induced Akt signaling and transcriptional factor CREB that are supposed to activate the neuroprotective mechanisms. On the other hand, DFS led to normalization of VGLUT1/2 expression and activity of Akt and CREB. Analysis of exocytosis proteins revealed the inhibition of SNAP-25, VAMP-2, and syntaxin 1 expression in DFS group proposing attenuation of excitatory neurotransmission. Thus, we revealed that short-term HU causes dysregulation of glutamatergic system of the hippocampus, but, at the same time, stimulates neuroprotective Akt-dependent mechanism. In addition, most importantly, we demonstrated positive effect of DFS on the hippocampus functioning that probably depends on the regulation of neurotransmitter exocytosis.

太空飞行和模拟微重力都会影响学习和记忆，而这主要是由海马体控制的。然而，有关真实或模拟微重力条件下海马体分子变化的数据是有限的。实验中招募了成年 Wistar 大鼠。在这里，我们分析了 3 天后肢卸载 (HU) 引起的短期模拟微重力是否会影响海马的谷氨酸能和 GABA 能系统，以及在 HU 期间对足底表面施加动态足部刺激 (DFS) 如何有助于调节海马体功能。结果表明，HU 3 天后海马中囊泡谷氨酸转运蛋白 1 和 2 (VGLUT1/2) 的表达下降，而谷氨酸脱羧酶 67 (GAD67) 的表达不受影响。 HU 还显着诱导 Akt 信号传导和转录因子 CREB，这些信号被认为可以激活神经保护机制。另一方面，DFS 导致 VGLUT1/2 表达以及 Akt 和 CREB ​​活性正常化。胞吐蛋白分析揭示了 DFS 组中 SNAP-25、VAMP-2 和 Syntaxin 1 表达的抑制，表明兴奋性神经传递减弱。因此，我们发现短期 HU 会导致海马谷氨酸能系统失调，但同时会刺激 Akt 依赖性神经保护机制。此外，最重要的是，我们证明了 DFS 对海马功能的积极影响，这可能取决于神经递质胞吐作用的调节。