Repetitive transcranial magnetic stimulation ameliorates recognition memory impairment induced by hindlimb unloading in mice associated with BDNF/TrkB signaling

Abstract

Repetitive transcranial magnetic stimulation (rTMS), which could improve learning and memory, is widely used in psychiatry and neurology as a therapeutic approach. There are few studies reporting effective countermeasures to cognition decline in astronauts during space flight. Accordingly, we examined whether rTMS was able to significantly alleviate the learning and memory deficits induced by hindlimb unloading (HU), a general accepted rodent model to simulate microgravity, in mice. Male C57BL/6 J mice were randomly divided into four groups: Sham, rTMS, HU, and HU + rTMS groups. The hindlimb unloading procedure continued for consecutive 14 days. Meanwhile, high frequency rTMS (15 Hz) was applied for 14 days from the 1st day of HU procedure. The novel object recognition test showed that the recognition memory was evidently impaired in the HU group compared to that in the Sham group, however, rTMS significantly attenuated the impairment of the memory. Furthermore, rTMS significantly improved the HU-induced LTP impairment and increased spine density in the hippocampal dentate gyrus region. Additionally, rTMS enhanced the expressions of postsynaptic function-associated proteins N-methyl-d-aspartic acid receptors (NR2B and NR2 A) and postsynaptic density protein (PSD95), upregulated BDNF/TrkB signaling and increased phosphorylation of protein kinase B (Akt) in the HU + rTMS group. In conclusion, the data suggest that high frequency rTMS may be an effective countermeasure against the learning and memory deficiency, induced by simulated microgravity.