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Puerarin Up-regulates Methyl-CpG Binding Protein 2 Phosphorylation in Hippocampus of Vascular Dementia Rats
Hu-Qing Wang1, Meng Zhang1, Jia-Xin Zhao1
1Department of Neurology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
Objective:
To observe the effect of puerarin on methyl-CpG binding protein 2 (MeCP2) phosphorylation (pMeCP2) in the hippocampus of a rat model of vascular dementia (VD).
Methods:
Thirty-six healthy Sprague-Dawley rats were randomly assigned to the sham-operated group, dementia group and puerarintreated group using a random number table (n=12 per group). The modifified permanent bilateral common carotid artery occlusion method was used to establish the VD model. The sham-operated and dementia groups were given 2 mL/d of saline, while the puerarin-treated group was given 100 mg/(kg•d) of puerarin for 17 days. The learning and memory abilities were evaluated by the Morris water maze test. Hematoxylin-eosin staining, immunohistochemical (IHC) staining and Western blot analysis were carried out to observe changes in neuron morphology and in level of pMeCP2 in the hippocampus, respectively.
Results:
The morphologies of rat hippocampal neurons in the puerarintreated group were markedly improved compared with the dementia group. The escape latency of the dementia group was significantly longer than the sham-operated group (P<0.05), while the puerarin-treated group was obviously shorter than the dementia group (P<0.05). Cross-platform times of the dementia group were signifificantly decreased compared with the sham-operated group (P<0.05), while the puerarin-treated group was obviously increased compared with the dementia group (P<0.05). IHC staining showed no significant difference in the number of MeCP2 positive cells among 3 groups (P>0.05). The number of pMeCP2 positive cells in the CA1 region of hippocampus in the dementia group was signifificantly increased compared with the sham-operated group, and the puerarin-treated group was signifificantly increased compared with the dementia group (both P<0.05). Western blot analysis showed no signifificant difference of MeCP2 expression among 3 groups (P>0.05). The expression of pMeCP2 in the dementia group was signifificantly increased compared with the sham-operated group, while it in the puerarin-treated group was signifificantly increased compared with the dementia group (P<0.05).
Conclusion:
Puerarin could play a role in the protection of nerve cells through up-regulating pMeCP2 in the hippocampus, improving neuron morphologies, and enhancing learning and memory ablities in a rat model of VD.
Insights
Puerarin treatment improved neuron morphology and enhanced learning and memory in a vascular dementia (VD) rat model. This neuroprotection is linked to increased methyl-CpG binding protein 2 (MeCP2) phosphorylation (pMeCP2) in the hippocampus.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Vascular dementia (VD) is a debilitating neurological condition characterized by cognitive decline.
- Methyl-CpG binding protein 2 (MeCP2) and its phosphorylation (pMeCP2) play crucial roles in neuronal function and plasticity.
- Understanding the molecular mechanisms underlying VD is essential for developing effective therapeutic strategies.
Purpose of the Study:
- To investigate the therapeutic effects of puerarin on cognitive deficits in a rat model of vascular dementia.
- To examine the impact of puerarin on methyl-CpG binding protein 2 (MeCP2) phosphorylation (pMeCP2) levels in the hippocampus of rats with VD.
- To assess changes in hippocampal neuron morphology and learning/memory abilities following puerarin treatment.
Main Methods:
- A rat model of vascular dementia was established using permanent bilateral common carotid artery occlusion.
- Rats were divided into sham-operated, VD, and puerarin-treated groups, receiving either saline or puerarin (100 mg/kg/day) for 17 days.
- Cognitive function was assessed using the Morris water maze test, and hippocampal tissues were analyzed for neuron morphology (H&E staining), MeCP2, and pMeCP2 expression (IHC and Western blot).
Main Results:
- Puerarin treatment significantly improved learning and memory in VD rats, evidenced by reduced escape latency and increased cross-platform times in the Morris water maze.
- Histological analysis revealed improved neuron morphology in the hippocampus of puerarin-treated rats compared to the VD group.
- While MeCP2 expression remained unchanged, puerarin administration significantly increased pMeCP2 levels in the hippocampus, particularly in the CA1 region, compared to the VD group.
Conclusions:
- Puerarin demonstrates significant neuroprotective effects in a rat model of vascular dementia.
- The therapeutic benefits of puerarin appear to be mediated, at least in part, by up-regulating hippocampal pMeCP2 levels.
- Puerarin enhances neuronal morphology and improves cognitive functions, suggesting its potential as a treatment for VD.
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