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Salidroside prevents gestational hypertension-induced impairment of offspring learning and memory via Wnt/Skp2
Qian Sun1, Li Zhang1, Xiuyan Huang1
1Department of Gynaecology and Obstetrics, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University Jinan, Shandong 250001, China.
Insights
Salidroside (Sal) improves learning and memory deficits in offspring from gestational hypertension (GHP). This neuroprotective effect is linked to Sal activating the Wnt1/Skp2 pathway, promoting neural stem cell growth.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Gestational hypertension (GHP) can impair offspring cognitive functions, specifically learning and memory.
- Salidroside (Sal), a known protective agent against diabetes-related impairments, was investigated for its potential in mitigating GHP-induced developmental issues.
Purpose of the Study:
- To investigate the therapeutic effect of Salidroside (Sal) on learning and memory impairments in offspring exposed to gestational hypertension (GHP).
- To elucidate the underlying molecular mechanisms, particularly the involvement of the Wnt1/Skp2 signaling pathway.
Main Methods:
- A rat model of GHP was established using NG-nitro-L-arginine methyl ester (L-NAME).
- Offspring cognitive function was assessed using the Morris Water Maze test.
- Hippocampal tissue was analyzed using HE staining, immunohistochemistry, immunofluorescence, and Western blot to evaluate pathological changes and protein expression.
Main Results:
- GHP offspring exhibited significantly impaired learning and memory compared to controls.
- Sal treatment notably improved cognitive function in GHP offspring.
- Sal increased Wnt1 and Skp2 expression while decreasing P27kiwf and P21waf1 in the hippocampus.
- Sal promoted neural stem cell proliferation and differentiation in vitro, an effect reversed by Wnt1 knockdown.
- Sal elevated Tuj1, SOX2, Ki67, and DCX protein levels in the GHP offspring hippocampus.
Conclusions:
- Salidroside effectively ameliorates learning and memory deficits in offspring affected by GHP.
- The mechanism involves Salidroside activating the Wnt1/Skp2 signaling pathway, which enhances neural stem cell proliferation and differentiation.
Background:
Salidroside (Sal) has been found to protect against multiple impairments caused by diabetes, and we designed this study to investigate the effect of Sal on gestational hypertension (GHP)-induced impairment of offspring learning and memory.
Methods:
We established a GHP rat model by intraperitoneal injection of NG-nitro-L-arginine methyl ester (L-NAME), and treated with Sal by daily gavage. We used Morris Water Maze test to evaluate the learning and memory ability of offspring rats. HE staining was used to measured the pathological changes in hippocampus of offspring. Immunohistochemistry, cellular immunofluorescence and western blot were used to detect the protein expression.
Results:
The learning and memory abilities of GHP offspring rats were significantly lower than those of normal rat offspring, while Sal treatment could significantly improve the learning and memory abilities of GHP offspring rats. HE staining did not reveal pathological differences in the hippocampus of normal rats, GHP rats and Sal-treated GHP offspring rats. However, Sal treatment can significantly increase the expression of Wnt1 and Skp2 protein, and decrease the expression of P27kiwf and P21waf1 protein in the hippocampus of GHP offspring rats. In vitro, Sal significantly promoted the proliferation and differentiation on neural stem cell, while Wnt1 knockdown could reverse these promotions by Sal. In the hippocampus of GHP offspring rats, Sal treatment significantly increased the expression of Tuj1, SOX2, Ki67 and DCX protein.
Conclusion:
Salidroside significantly improves the learning and memory impairment of offspring caused by GHP, and its mechanism may be related to the fact that Salidroside promotes the proliferation and differentiation of neural stem cells by activating the Wnt1/Skp2 signaling pathway.
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