Effects Of Glycosides Of Cistanche On Learning Cognitionand Synaptic Plasticity in Sleep Deprivation Model Rats Ⅱ

2 results

2． 1 Effect of GCs on learning and memory in rats

2． 1． 1 Positioning navigation experiment

As the number of days of positioning and navigation training increased, the escape latency of rats in each group decreased, and the decrease was most obvious at 2 to 3 days. As time went by, the escape latency of rats in the Model group maintained a stable state, while the Control group and PC The escape latency of rats in the group, GCs group, and Est group gradually decreased. See Figure 1.

HIGH GLYCOSIDE CISTANCHE SUPPLEMENTS FOR IMPROVING MEMORY

2． 1． 2 Space exploration experiments

Compared with the Control group, the number of times rats in the Model group crossed the platform and the percentage of time spent in the target quadrant were significantly reduced (P < 0.01). There was no statistically significant difference between the PC group and the Model group, indicating that the sleep deprivation model was successful. Compared with the Model group, the number of times the rats in the GCs group crossed the platform and the percentage of time spent in the target quadrant increased significantly (P < 0.. 01), while the difference in the Est group was not statistically significant; compared with the GCs group, the number of times the rats in the Est group crossed the platform increased significantly (P < 0. 01). and the percentage of residence time in the target quadrant was significantly reduced (P < 0. 01). See Figure 2.

2． 2. Effect of GCs on anxiety behavior in rats

The results of the open-field experiment showed that It shows that compared with the Control group, the number of standing and movements of the rats in the Model group were The distance increased significantly (P ＜ 0. 05), the resting time decreased significantly (P ＞ 0. 01), and there was no statistically significant difference between the PC group and the Control group (P ＞ 0. 05). Compared with the Model group, GCs treatment can significantly reduce the standing frequency and movement distance of the rats in the Model group (P ＜ 0. 05), and significantly increase the immobility time (P ＜ 0. 05). After treatment with Est, the difference between el group comparison The difference was not statistically significant (P > 0. 05). See Table 2.

Figure 2 Results of the space exploration experiment

Note: A: number of platform crossings; B: percentage of time spent in the target quadrant; compared with the Control group, ∗P < 0.05, ∗∗P < 0.01; compared with the Model group, ＃＃P < 0.01

Table 2 Effects of GCs on anxiety behavior in rats (x ± s)

Table 3 Effects of GCs on serum MT levels in rats (x ± s)

2.4 Effect of GCs on the morphology and number of cells in the CA1 region of the hippocampus of rats In the Control group and PC group, the neurons in the CA1 region of the hippocampus were neatly arranged, with clear nuclei, centrally located nucleoli, and uniform coloring; compared with the Control group, the Nissl bodies of the rats in the Model group were loosely arranged, with larger gaps and fewer numbers (P < 0.05), and the cells were atrophied, with a large number of vacuoles, and some Nissl bodies were binucleated or multinucleated; compared with the Model group, after GCs treatment, the Nissl bodies were neatly arranged, with an increased number, and vacuoles were visible in a small number; no significant changes were observed in the Est group compared with the Model group. See Figure 3, Table 4.

Table 4. Nissl staining and counting of neuronal cell numbers in the hippocampal CA1 region

2． 5 Effects of GCs on the expression of synapse-related molecular markers in rats

2． 5． 1 Effect of GCs on BDNF, SYN, and PSD-95 protein expression in rat hippocampus. Western blot experiment results showed that, with

Compared with the Control group, the BDNF, SYN, and PSD-95 protein expression levels in the Model group were significantly reduced (P < 0. 01), and the PC group was significantly different from the C group. The difference between the control group and the control group was not statistically significant. Compared with the Model group, GCs could significantly up-regulate BDNF, SYN, and PSD-95 protein expression (P < 0. 01), while Est supplementation treatment did not affect BD. There was no significant change in the expression of NF, SYN, and PSD-95 proteins. See Figure 4.

2． 5． 2. Effect of GCs on BDNF, SYN, and PSD-95mRNA expression in rat hippocampus. RT-PCR experimental results showed that compared with the Control group, The expression levels of BDNF, SYN, and PSD-95 mR⁃ＮＡ in the Model group were significantly reduced (P ＜ 0 .01), and there was no significant difference between the PC group and the Control group. Compared with the Model group, GCs could significantly up-regulate the expression levels of BDNF, SYN, and PSD-95 mRNA (P <0. 01), while Est BDNF, SYN, and PSD - 95 mRNA table

There was no significant impact on the level. See Figure 5.

Note: A: BDNF protein expression; B: SYN protein expression; C: PSD-95 protein expression; compared with Control group, ∗P < 0.05, ∗∗P < 0.01; compared with Model group, ＃P < 0.05, ＃#P < 0.01; compared with GCs group, ※P < 0.05

3 Discussion

Good sleep helps the body grow and develop, improves learning efficiency, and promotes memory consolidation [7]. Lack of sleep can lead to memory impairment, slow reactions, and cognitive decline. Cistanche deserticola is a traditional and precious Chinese herbal medicine, known as the "desert ginseng". Its chemical components mainly include phenylethanol glycosides, cyclopentane ether terpenes, polysaccharides, and volatile components. Among them, polysaccharides have attracted widespread attention due to their biological activities such as regulating immune activity, anti-aging, and anti-tumor [8].

Related studies have reported that GCs play a neuroprotective role such as antioxidant and anti-apoptotic, and effectively improve the neurological function of ischemic stroke mice [9]. More and more studies have found that GCs have a huge potential in inhibiting the progression of neurodegenerative diseases [10]. Related studies have reported that Cistanche deserticola phenylethanol glycosides (PhGs) inhibit TLR4/NF-κB signal transduction pathways, reduce neuroinflammation, enhance the expression of p-CAMKII/CAMKII to a certain extent, increase the expression level of synaptic-related proteins, and improve the learning and memory ability of APP/PS1 mice [11].

Previous studies by our research group also found that PhGs can play an antioxidant role, increase the protein expression level of SYN and PSD-95, regulate synaptic plasticity, and thus improve the learning and cognitive defects of SAMP8 mice [4].

This experiment constructed a rat sleep deprivation model by improving the multi-platform water environment method to explore whether GCs affect synaptic plasticity by regulating the expression of synaptic-related markers and thus improve the learning and cognitive function of rats in the sleep deprivation model. Melatonin (MT) is an endocrine hormone synthesized and secreted by the pineal gland under normal light and dark conditions at night that regulates circadian rhythms. It plays an important physiological function in controlling sleep and circadian rhythms. Melatonin rhythm disorders are the main factor behind sleep and circadian rhythm disorders [12].

The results of the serum ELISA test in this experiment showed that sleep deprivation caused a decrease in MT levels in model rats, and disrupted the sleep rhythm of rats, and the sleep deprivation model was successfully established. This study found that GCs can significantly shorten the escape latency of sleep deprivation model rats and increase the number of platform crossings, suggesting that GCs can effectively improve the learning and memory function of sleep deprivation model rats. Previous studies have reported that SD not only causes cognitive dysfunction but also may increase negative emotions such as anxiety and irritability in rats [13].

The results of this study showed that sleep deprivation can increase the number of standing times and movement distance of rats, and aggravate the tension and anxiety of model rats, which is consistent with previous research reports. After GC intervention, the number of standing times of rats decreased, the immobility time increased, and the movement distance decreased, which indicates that GCs can effectively improve the anxiety of sleep deprivation model rats.

Synapses are inseparable from learning and cognitive functions. The plasticity of synaptic structure and function is an important biological basis for the body's learning and memory ability [14]. The expression of synapse-related proteins plays an important role in the regulation of synaptic plasticity. SYN is a special glycoprotein of the presynaptic membrane that can regulate the extension of synapses and promote the forward movement of synaptic vesicles. It is considered to be a marker protein for the development and activity of the presynaptic membrane [15].

BDNF is one of the most characteristic neurotrophic factors. It regulates the growth and differentiation of neurons and plays an important role in the formation of synaptic plasticity [16]. PSD-95 plays an indispensable role in maintaining the stability of synaptic structure and promoting the efficiency of synaptic transmission [17]. Previous literature reports that sleep deprivation can cause oxidative damage to hippocampal neurons and abnormal expression of synaptic-related proteins, leading to decreased synaptic plasticity and inducing learning and cognitive dysfunction [18].

This experimental study found that the expression levels of SYN, PSD-95, and BDNF in the hippocampus of sleep deprivation model rats were significantly reduced, which is consistent with the results of previous studies. After administration of GCs, the expression levels of SYN, PSD-95, and BDNF increased, indicating that GCs can increase the expression level of synaptic-related proteins and thus improve synaptic plasticity and memory function of model rats.

In summary, GCs may affect synaptic plasticity by regulating the expression of synaptic-related markers, thereby improving SD-induced learning and cognitive function, which will provide new treatment ideas and solutions for GCs to treat learning and cognitive impairment caused by sleep disorders.

References 

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