EGB761 ameliorates chronic cerebral hypoperfusion-induced cognitive dysfunction and synaptic plasticity impairment.

Abstract

Chronic cerebral hypoperfusion (CCH) may lead to the cognitive dysfunction, but the underlying mechanisms are unclear. EGB761, extracted from Ginkgo biloba and as a phytomedicine widely used in the world, has been showed to have various neuroprotective roles and mechanisms, and therapeutic effects in Alzheimer's disease and other cognitive dysfunctions. However, improvements in cognitive function after CCH, following treatment with EGB761, have not been ascertained yet. In this study, we used the behavior test, electrophysiology, neurobiochemistry, and immunohistochemistry to investigate the EGB761's effect on CCH-induced cognitive dysfunction and identify its underlying mechanisms. The results showed that EGB761 ameliorates spatial cognitive dysfunction occurring after CCH. It may also improve impairment of the long-term potentiation, field excitable potential, synaptic transmission, and the transmission synchronization of neural circuit signals between the entorhinal cortex and hippocampal CA1. EGB761 may also reverse the inhibition of neural activity and the degeneration of dendritic spines and synaptic structure after CCH; it also prevents the downregulation of synaptic proteins molecules and pathways related to the formation and stability of dendritic spines structures. EGB761 may inhibit axon demyelination and ameliorate the inhibition of the mTOR signaling pathway after CCH to improve protein synthesis. In conclusion, EGB761 treatment after CCH may improve spatial cognitive function by ameliorating synaptic plasticity impairment, synapse degeneration, and axon demyelination by rectifying the inhibition of the mTOR signaling pathway.

• Authors: Zhao-Hui Yao, Jing Wang, Jing-Ping Yuan, Kai Xiao, Shao-Feng Zhang, Yan-Chun Xie, Jun-Hua Mei
• Journal: Aging (Aging (Albany NY)) Vol. 13 Issue 7 Pg. 9522-9541 (02 03 2021) ISSN: 1945-4589 [Electronic] United States
• PMID: 33539323 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neuroprotective Agents
• Plant Extracts
• Ginkgo biloba extract

Topics

• Animals
• Brain Ischemia (complications, metabolism)
• Cognitive Dysfunction (drug therapy, etiology, metabolism)
• Dendritic Spines (drug effects, metabolism)
• Ginkgo biloba
• Male
• Maze Learning (drug effects)
• Neuronal Plasticity (drug effects)
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Plant Extracts (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Synapses (drug effects, metabolism)