Protective effects of ginsenosides Rg1 and Rb1 against cognitive impairment induced by simulated microgravity in rats

OBJECTIVE Microgravity exerts several negative effects on the learning and memory of astronauts during space flight. Rg1 and Rb1, the key steroidal components of ginseng, have shown potent neuroprotective effects with a high safety profile. The object of the current study is to investigate the influence of Rg1 and Rb1 on simulated microgravity-induced memory and learning dysfunction in the hindlimb suspension(HLS) rat model. METHODS The HLS rats were orally administered Rg1(30 and 60 μmol·kg-1) or Rb1(30 and 60 μmol·kg-1)for four weeks. The Morris water maze test(MWM) and reward operating conditioning reflex test(ROCR) were conducted to evaluate spatial and associative learning and memory. After the behavior tests, the serum and the prefrontal cortex(PFC)were dissected to measure the mechanism. RESULTS Rg1 and Rb1 treatment ameliorated the cognitive deficits of HLS-exposure rats in MWM and ROCR, reduced reactive oxygen species generation and increased antioxidant enzyme activity. Rg1 and Rb1also assisted in the recovery of mitochondrial complexⅠ(NADH dehydrogenase) activities and Mfn2, and decreased Drp-1 expression. Furthermore, Rg1 and Rb1 reduced the ratio of Bax/Bcl-2 and the expression of cleaved-caspase 3, cytochrome c, increased the levels of SYN, PSD95and activated BDNF-TrkB/PI3K-Akt pathway in the PFC.CONCLUSION Rg1 and Rb1 treatment attenuated cognitive deficits induced by HLS, mitigated mitochondrial dysfunction, attenuated oxidative stress, inhibited apoptosis, and increased the synaptic plasticity, which was partly mediated by the modulation of the BDNF-TrkB/PI3K-Akt signaling.