Brain and behavior · 2026
RTMS Mitigates Simulated Spaceflight-Induced Emotional Dysfunction Through VEGFR-2-Mediated Neuroprotection.
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Liang Rong, Xu Qing, Ren Jing, Wang Ling, Cheng Xinyan, Zhao Fei, Xu Jing, Yang Jiajia, Ming Dong
Аннотация
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.
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.