Rapamycin relieves anxious emotion and synaptic plasticity deficits induced by hindlimb unloading in mice

This study examined whether increasing autophagy could improve cognitive deficits in hindlimb unloaded (HU) mice, which was used as an animal model of synaptic plasticity impairment. Male C57BL/6 mice were randomly divided into three groups: control, HU and HU + rapamycin groups. Hindlimb unloading treatment was used to establish the animal model for 2 weeks. Rapamycin was intraperitoneally injected at a dose of 0.5 mg/kg/day along with hindlimb unloading procedure. The open field test and the elevated plus maze test showed that rapamycin considerably prevented the level of anxiety and increased exploratory behaviour in HU mice. Afterwards, long-term potentiation (LTP) recorded in the hippocampal dentate gyrus (DG) region was effectively reduced by rapamycin, which was significantly inhibited by HU procedure. In addition, rapamycin further increased the autophagy level, which was already elevated in HU mice. Meanwhile, the expression of NMDA receptor 2A and 2 B was modified by rapamycin in HU mice. Moreover, rapamycin noticeably increased the total superoxide dismutase (T-SOD) activity and reduced the malondialdehyde (MDA) as well as the level of carbonylated proteins in HU mice's hippocampus. The results show that increasing autophagy may pacificate the anxious emotion, and partly alleviate the hippocampal synaptic plasticity deficits.