rTMS pre-treatment effectively protects against cognitive and synaptic plasticity impairments induced by simulated microgravity in mice.

During space flight, microgravity has several negative effects on cognitive functions and learning and memory abilities. However, there are few effectively preventive methods that have been developed yet. Previous studies showed that repetitive transcranial magnetic stimulation (rTMS), as a novel non-invasive technique, alleviated cognitive dysfunctions and facilitated synaptic plasticity. In the present study, we used a hindlimb unloading (Hu) mouse model to simulate microgravity conditions. And then, we investigated whether rTMS played a neuroprotective role in a Hu mouse model. Behavioral experiments including Open field test and Novel object recognition test were performed. These results showed that spontaneous activity and recognition memory were reduced by Hu, while rTMS significantly protected against the harmful effect. Furthermore, electrophysiological recordings were performed to examine the level of synaptic plasticity including paired-pulse facilitation (PPF) and long-term potentiation (LTP). In the hippocampus DG and CA1 regions, dendritic spine density was measured using Golgi-Cox staining. Our data showed that rTMS effectively impeded the impairment of PPF and LTP, as well as the decrease of spine density induced by Hu. Subsequently, Western blot assay showed that rTMS inhibited the downregulation of CREB/BDNF signaling network associated proteins in Hu mice. It suggests that rTMS pre-treatment plays a neuroprotective role in protecting against cognitive impairments and synaptic plasticity deficits induced by microgravity stimulation.