Study on the role and mechanism of Tan IIA in Alzheimer's disease based on CREB-BDNF-TrkB pathway

Xiyong Xiang; Siyu Xia; Shan Li; Yirong Zeng; Lixuan Wang; Yan Zhou

doi:10.1016/j.neulet.2024.137769

Study on the role and mechanism of Tan IIA in Alzheimer's disease based on CREB-BDNF-TrkB pathway

Neurosci Lett. 2024 Apr 12:830:137769. doi: 10.1016/j.neulet.2024.137769. Online ahead of print.

Authors

Xiyong Xiang¹, Siyu Xia¹, Shan Li², Yirong Zeng¹, Lixuan Wang¹, Yan Zhou³

Affiliations

¹ College of Pharmacy, Guangxi Medical University, Nanning 530021, China.
² College of Nursing, Guangxi Medical University, Nanning 530021, China.
³ College of Pharmacy, Guangxi Medical University, Nanning 530021, China; Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Guangxi Medical University, Nanning 530021, China. Electronic address: zhouyan@gxmu.edu.cn.

PMID: 38616003
DOI: 10.1016/j.neulet.2024.137769

Abstract

The occurrence and development of Alzheimer's disease (AD) is closely related to neuronal loss, inflammatory response, cholinergic imbalance, and Tau protein hyperphosphorylation. Previous studies have confirmed that Streptozotocin (STZ) can be used to establish a rat model of AD by injecting it into the rat brain via the lateral ventricle. Our previous research showed that Danshentone IIA (Tan IIA) can improve cognitive dysfunction in rats caused by CC chemokine ligand 2, and network pharmacology results show that Tan IIA is very likely to improve AD symptoms through the cyclic adenosine monophosphate response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), and tyrosine kinase receptor protein (TrkB) pathway. The results of the water maze experiment showed that after Tan IIA treatment, the escape latency of AD rats was shortened and the number of platform crossings increased; in the new object recognition experiment, the discrimination index of AD rats significantly increased after treatment; Nissl staining and Tunel staining results showed that Tan IIA increased the number of surviving neurons in the hippocampus of cognitively impaired rats and reduced neuronal apoptosis; Bielschowsky silver staining results showed that Tan IIA reduced neurofibrillary tangles (NFTs) in the AD rats; Tan IIA can reduce the inflammatory response and oxidative stress reaction in the hippocampus of AD rats, and at the same time reduce the activity of acetylcholinesterase. Tan IIA can significantly increase the expression of CREB, BDNF, TrkB in the hippocampal tissue of STZ-injured rats (P < 0.05). These data suggest that Tan IIA may upregulate the expression of the CREB-BDNF-TrkB signaling pathway in the hippocampus of brain tissue, produce anti-neuroinflammatory, antioxidant stress, inhibit neuronal apoptosis effects, and improve cholinergic neurotransmitter disorder induced by STZ, reduce the neuronal damage and learning and memory impairment caused by STZ in rats, and improve the cognitive function of rats.

Keywords: BDNF; CREB; Cell apoptosis; Cognitive impairment; STZ; Tanshinone IIA; TrkB.