RTMS Mitigates Simulated Spaceflight‐Induced Emotional Dysfunction Through VEGFR‐2‐Mediated Neuroprotection
Rong Liang, Qing Xu, Jing Ren, Ling Wang, Xinyan Cheng, Fei Zhao, Jing Xu, Jiajia Yang, Dong MingABSTRACT
Purpose
Repetitive transcranial magnetic stimulation (rTMS) has shown potential in mitigating emotional deficits induced by extreme environments, such as those encountered during spaceflight. However, its underlying molecular mechanisms remain poorly understood. This study investigates the role of vascular endothelial growth factor receptor 2 (VEGFR‐2) in mediating the therapeutic effects of rTMS in a mouse model of simulated space composite environment (SSCE).
Method
10 Hz rTMS treatment was initiated after the last two weeks of SSCE exposure and continued for the remaining 2 weeks. Throughout the rTMS treatment period, the VEGF receptor antagonist SU5416 was co‐administered via intraperitoneal injection.
Finding
Behavioral tests revealed that VEGFR‐2 inhibition abolished the beneficial effects of rTMS on depressive‐ and anxiety‐like behaviors, as measured by the tail suspension, forced swim, sucrose preference, and elevated plus maze tests. Furthermore, SU5416 blocked rTMS‐induced improvement in social skills. At the cellular level, VEGFR‐2 antagonism impaired axonal integrity in the prefrontal cortex.
Conclusion
These findings suggest that VEGFR‐2 signaling is critical for the neuroprotective and behavioral benefits of rTMS under simulated spaceflight conditions, highlighting its potential as a therapeutic target for emotional regulation in extreme environments.