Youzhi Ning, Yue Zhang, Tao Jiang, Jianguo Feng, Jian Zhan, Cehua Ou, Lu Wang
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LRP1-mediated p-tau propagation contributes to cognitive impairment after chronic neuropathic pain in rats.
Trigeminal neuralgia (TN) is a prevalent chronic neuropathic pain syndrome characterized by severe pain, often accompanied by cognitive dysfunction and cerebral degeneration. However, its mechanisms remain poorly understood. Hyperphosphorylation of tau protein (p-tau) is often seen in neurodegenerative disorders such as Alzheimer's disease (AD). LRP1 expression on brain neurons and microglial cells is believed to facilitate the propagation of p-tau. We established a TN rat model via infraorbital nerve chronic constrictive injury (ION-CCI). Once the model was established, we investigated the association between p-tau and cognitive impairment in TN rats by evaluating behavioral and degenerative markers. During the initial phase, we noted an increase in p-tau level in the prefrontal cortex and hippocampal tissues of TN rats. The accompanied impaired learning and memory abilities suggested cognitive dysfunction. Blocking p-tau synthesis by orally administering a protein phosphatase and by injecting adenoviral vectors targeting LRP1 into the lateral ventricle of rats ameliorated cognitive impairment. This suggests that cognitive decline in TN rats is linked to elevated p-tau levels. Our findings show that LRP1-mediated p-tau propagation may drive cognitive impairment associated with neuropathic pain in TN rats.
期刊介绍:
The international journal publishing original full-length research articles, short communications, technical notes, and reviews on all aspects of neuroscience
Neuroscience Research is an international journal for high quality articles in all branches of neuroscience, from the molecular to the behavioral levels. The journal is published in collaboration with the Japan Neuroscience Society and is open to all contributors in the world.