Microgravity experienced during space flight is known to exert several negative effects on the learning ability and memory of astronauts. Few effective strategies are currently available to counteract these effects. Rg1 and Rb1, the major steroidal components of ginseng, have shown potent neuroprotective effects with a high safety profile. The present study aimed to investigate the effects of Rg1 and Rb1 on simulated microgravity-induced learning and memory dysfunction and its underlying mechanism in the hindlimb suspension (HLS) rat model. Administration of Rg1 (30 and 60 μmol/kg) and Rb1 (30 and 60 μmol/kg) for 2 weeks resulted in a significant amelioration of impaired spatial and associative learning and memory caused by 4-week HLS exposure, measured using the Morris water maze and Reward operating conditioning reflex (ROCR) tests, respectively. Furthermore, Rg1 and Rb1 administration alleviated reactive oxygen species production and enhanced antioxidant enzyme activities in the prefrontal cortex (PFC). Rg1 and Rb1 also assisted in the recovery of mitochondrial complex I (NADH dehydrogenase) activities, increased the expression of Mfn2 and decreased the fission marker dynamin-related protein (Drp)-1expression. Additionally, Rg1 and Rb1 treatment increased the SYN, and PSD95 protein expressions and decreased the ratio of Bax:Bcl-2 and reduced the expression of cleaved caspase-3 and cytochrome C. Besides these, the BDNF-TrkB/PI3K-Akt pathway was also activated by Rg1 and Rb1 treatment. Altogether, Rg1 and Rb1 treatment attenuated cognitive deficits induced by HLS, mitigated mitochondrial dysfunction, attenuated oxidative stress, inhibited apoptosis, increased synaptic plasticity, and restored BDNF-TrkB/PI3K-Akt signaling.
In aerospace medicine, the influence of microgravity on cognition has always been a risk factor threatening astronauts’ health. The traditional medicinal plant and food material Gastrodia elata Blume has been used as a therapeutic drug for neurological diseases for a long time due to its unique neuroprotective effect. To study the effect of fresh Gastrodia elata Blume (FG) on cognitive impairment caused by microgravity, hindlimb unloading (HU) was used to stimulate weightlessness in mice. The fresh Gastrodia elata Blume (0.5 g/kg or 1.0 g/kg) was intragastrically administered daily to mice exposed to HU and behavioral tests were conducted after four weeks to detect the cognitive status of animals. The behavioral tests results showed that fresh Gastrodia elata Blume therapy significantly improved the performance of mice in the object location recognition test, Step-Down test, and Morris Water Maze test, including short-term and long-term spatial memory. According to the biochemical test results, fresh Gastrodia elata Blume administration not only reduced serum factor levels of oxidative stress but also maintained the balance of pro-inflammatory and anti-inflammatory factors in the hippocampus, reversing the abnormal increase of NLRP3 and NF-κB. The apoptosis-related proteins were downregulated which may be related to the activation of the PI3K/AKT/mTOR pathway by fresh Gastrodia elata Blume therapy, and the abnormal changes of synapse-related protein and glutamate neurotransmitter were corrected. These results identify the improvement effect of fresh Gastrodia elata Blume as a new application form of Gastrodia elata Blume on cognitive impairment caused by simulated weightlessness and advance our understanding of the mechanism of fresh Gastrodia elata Blume on the neuroprotective effect.
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