Berezovskaya Anna S, Tyganov Sergey A, Nikolaeva Svetlana D, Naumova Alexandra A, Merkulyeva Natalia S, Shenkman Boris S, Glazova Margarita V
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez pr., 194223, St.Petersburg, Russia.
Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia.
Cell Mol Neurobiol. 2021 Oct;41(7):1549-1561. doi: 10.1007/s10571-020-00922-2. Epub 2020 Jul 18.
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，而学习和记忆大多由海马体控制。然而，关于在真实或模拟微重力条件下海马体分子变化的数据有限。实验招募了成年Wistar大鼠。在此，我们分析了3天的后肢卸载（HU）所导致的短期模拟微重力是否会影响海马体的谷氨酸能和γ-氨基丁酸能系统，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天后海马体中囊泡谷氨酸转运体1和2（VGLUT1/2）的表达降低，而谷氨酸脱羧酶67（GAD67）的表达未受影响。HU还显著诱导了理应激活神经保护机制的Akt信号传导和转录因子CREB。另一方面，DFS导致VGLUT1/2表达以及Akt和CREB的活性恢复正常。对胞吐蛋白的分析显示，DFS组中SNAP-25、VAMP-2和 syntaxin 1的表达受到抑制，提示兴奋性神经传递减弱。因此，我们发现短期HU会导致海马体谷氨酸能系统失调，但同时会刺激依赖Akt的神经保护机制。此外，最重要的是，我们证明了DFS对海马体功能有积极作用，这可能取决于对神经递质胞吐作用的调节。
