Time-course adaptive changes in hippocampal transcriptome and synaptic function induced by simulated microgravity associated with cognition

Rong Liang; Ling Wang; Qing Yang; Qing Xu; Shufan Sun; Haichen Zhou; Meiling Zhao; Jing Gao; Chenguang Zheng; Jiajia Yang; Dong Ming

doi:10.3389/fncel.2023.1275771

Time-course adaptive changes in hippocampal transcriptome and synaptic function induced by simulated microgravity associated with cognition

Front Cell Neurosci. 2023 Oct 5:17:1275771. doi: 10.3389/fncel.2023.1275771. eCollection 2023.

Authors

Rong Liang^#¹, Ling Wang^#^{1

2

3}, Qing Yang¹, Qing Xu¹, Shufan Sun¹, Haichen Zhou¹, Meiling Zhao¹, Jing Gao¹, Chenguang Zheng^{1

2

3}, Jiajia Yang^{1

2

3}, Dong Ming^{1

2

3}

Affiliations

¹ Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China.
² Tianjin Key Laboratory of Brain Science and Neuroengineering, Tianjin, China.
³ Haihe Laboratory of Brain-Computer Interaction and Human-Machine Integration, Tianjin, China.

^# Contributed equally.

Abstract

Introduction: The investigation of cognitive function in microgravity, both short-term and long-term, remains largely descriptive. And the underlying mechanisms of the changes over time remain unclear.

Methods: Behavioral tests, electrophysiological recording, and RNA sequencing were used to observe differences in behavior, synaptic plasticity, and gene expression.

Results: Initially, we measured the performance of spatial cognition exposed to long-term simulated microgravity (SM). Both working memory and advanced cognitive abilities were enhanced. Somewhat surprisingly, the synaptic plasticity of the hippocampal CA3-CA1 synapse was impaired. To gain insight into the mechanism of changing regularity over time, transcriptome sequencing in the hippocampus was performed. The analysis identified 20 differentially expressed genes (DEGs) in the hippocampus after short-term modeling, 19 of which were up-regulated. Gene Ontology (GO) analysis showed that these up-regulated genes were mainly enriched in synaptic-related processes, such as Stxbp5l and Epha6. This might be related to the enhancement of working memory performance under short-term SM exposure. Under exposure to long-term SM, 7 DEGs were identified in the hippocampus, all of which were up-regulated and related to oxidative stress and metabolism, such as Depp1 and Lrg1. Compensatory effects occurred with increased modeling time.

Discussion: To sum up, our current research indicates that the cognitive function under SM exposure is consistently maintained or potentially even being enhanced over both short and long durations. The underlying mechanisms are intricate and potentially linked to the differential expression of hippocampal-associated genes and alterations in synaptic function, with these effects being time-dependent. The present study will lay the experimental and theoretical foundation of the multi-level mechanism of cognitive function under space flight.

Keywords: RNA sequencing; cognition; hippocampus; simulated microgravity; synaptic plasticity.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the National Natural Science Foundation of China (82371886, T2322021, 82202797, 82271218, and 81925020), the Lingang Laboratory (LG-TKN-202204-01), and the China Post-doctoral Science Foundation (2022M712365).