Dihydromyricetin affects BDNF levels in the nervous system in rats with comorbid diabetic neuropathic pain and depression

Yuanzhen Hao,Yun Gao,Yulin Shen,Huixiang Ge,Lingkun He,Wei Xiong,Shu Guan,Ruoyu Huang,Cancan Yin,Lijuan Liu,Mengyun Sun

doi:10.1038/s41598-019-51124-w

Yuanzhen Hao, Yun Gao + Show 9 more

Open Access

https://doi.org/10.1038/s41598-019-51124-w

Copy DOI

Abstract

Diabetic neuropathic pain (DNP) and depression (DP) are the common complications in patients with diabetes. The purpose of our research was to observe whether brain-derived neurotrophic factor (BDNF) levels and tropomyosin receptor kinase B (TrkB) in the nervous system have effects on rats with comorbid DNP and DP, and to determine whether dihydromyricetin (DHM) may influence BDNF/ TrkB pathway to mitigatethe comorbidity. The study showed that DHM treatment could attenuates pain and depressive behavior in DNP and DP combined rats. Compared with the control group, the expression level of BDNF/TrkB in the hippocampus of DNP + DP group were reduced, while the expression levels in the spinal cord and DRG were increased. However, after treatment with DHM, those changes were reversed. Compared with the control group, the level of IL-1β and TNF-α in the hippocampus, spinal cord and DRG in the DNP + DP group was significantly increased, and DHM treatment could reduce the increase. Thus our study indicated that DHM can relief symptoms of DNP and DP by suppressing the BDNF/TrkB pathway and the proinflammatory factor, and BDNF/TrkB pathway may be an effective target for treatment of comorbid DNP and DP.

Highlights

Diabetes is a clinically chronic disease, and by 2045, the estimated worldwide incidence will rise to 693 million people[1]
There were no differences in thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) between the control group and the control + DHM group (p > 0.05)
The results showed that in DRG and spinal cord tissue, the mRNA and protein expression levels of brain-derived neurotrophic factor (BDNF) and Tropomyosin receptor kinase B (TrkB) were higher in the Diabetic neuropathic pain (DNP) + DP group than in the control group (Control) group, but in thehippocampus, the expression levels of BDNF and TrkB in the DNP + DP group were lower than in the Control group (p < 0.01)

Summary

Introduction

Diabetes is a clinically chronic disease, and by 2045, the estimated worldwide incidence will rise to 693 million people[1]. It is especially important to seek more effective treatments. Some patients may have the comorbid conditions of DNP and DP, and the comorbidity brings more serious physical and mental effects to patients, and is more difficult to treat than only one disorder[10]. It is extremely urgent to seek more effective treatments. BDNF is a key signalling molecule in the microglia-neuron signalling pathway, and may be a therapeutic strategy for neuropathic pain treatment[14]. BDNF in the hippocampus mediated the antidepressant-like effects of conventional antidepressants and ketamine, which makes BDNF an important target for depression[15]. In comorbid DNP and DP conditions, the role of BDNF/TrkB pathway in the nervous system remains unclear and requires further research

Objectives

Methods

Results

Conclusion