Plasma BDNF and TrkB mRNA in PBMCs Are Correlated With Anti-depressive Effects of 12-Weeks Supervised Exercise During Protracted Methamphetamine Abstinence.

Jue Yang,Qiu Fang Li,Yi Liu,Jin Xiu Li,Xu Luo,Jun Zhang,Chun Xia Lu,Dan Cheng,Lan Zheng,Wen Qi Hou,Jun Tan

doi:10.3389/fnmol.2020.00020

Abstract

Purpose: The aim of this study was to evaluate the potential neurotrophic factors and expression of neurotrophin receptors in peripheral blood mononuclear cells linked with the antidepressant action of exercise intervention during protracted methamphetamine (METH) abstinence.Materials and Methods: A total of 72 male METH addicts, including 47 individuals with depression and 25 individuals without depression, were recruited in this study. Individuals with depression were divided into the depression control group and the depression exercised group. Consequently, 12 weeks of supervised exercise intervention was applied. Depression and anxiety were analyzed; plasma brain-derived neurotrophic factor (BDNF), neuronal growth factor (NGF), neurotrophin-3 (NT-3), NT-4, and proBDNF levels were tested using enzyme-linked immunosorbent assay; the mRNA expressions of TrkA, TrkB-FL, TrkB-T1, TrkCB, and P75NTR in peripheral blood mononuclear cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR).Results: NT-4 plasma levels were correlated with depression (r = −0.330, p = 0.005), which remained significant after Bonferroni correction. In addition, the BDNF and NT-3 levels in the plasma were significantly correlated with depression (r = −0.268, p = 0.023; r = −0.259, p = 0.028), but did not reach significance after Bonferroni correction. The BDNF, NT-3, and NT-4 plasma levels were significantly different between the depressive control group and the depressive exercise group using pre-exercise values as the covariate. The fold changes in TrkB-FL and TrkB-T1 mRNA in peripheral blood mononuclear cells between the post-exercise and pre-exercise demonstrated a remarkable decrease (fold change = −11.056 and −39.055).Conclusions: Exercise intervention can alleviate depression and anxiety during protracted METH abstinence. Decrease in BDNF and the expression of TrkB in peripheral blood mononuclear cells occur following the exercise intervention.

Highlights

Depression and anxiety are the most prominent psychiatric complaints reported by methamphetamine (METH) users (Glasner-Edwards and Mooney, 2014; Bagheri et al, 2015)
These data provide new evidence that structural regular exercise can decrease the brain-derived neurotrophic factor (BDNF), NT-3, and NT-4 plasma levels that are correlated with the alleviation of depression and anxiety after METH withdrawal
These results revealed that 12-week exercise training could be attributed to improved depressive symptoms of METH withdrawal, which was correlated with the BDNF-TrkB pathway in peripheral blood mononuclear cells

Summary

Introduction

Depression and anxiety are the most prominent psychiatric complaints reported by methamphetamine (METH) users (Glasner-Edwards and Mooney, 2014; Bagheri et al, 2015). A growing evidence has suggested that neurotrophin, and especially brain-derived neurotrophic factor (BDNF), is important in anxiety and depression. The neurotrophin family includes four different members, including neuronal growth factor (NGF) (Cohen et al, 1954), BDNF (Barde et al, 1982), neurotrophin-3 (NT-3) (Maisonpierre et al, 1990), and neurotrophin-4/5 (NT-4/5) (Berkemeier et al, 1991; Ip et al, 1992). All members of the neurotrophin family bind to pan-neurotrophin receptor p75NTR with low affinity (Johnson et al, 1986; Radeke et al, 1987). Only mature neurotrophins, which bind to different tropomyosin-related kinase (Trk) receptors with high affinity, exhibit ligand selectivity. Pro-neurotrophins (immature form of neurotrophin), such as proBDNF, proNGF, and proNT-3, have been found to function via interaction with p75NTR (Fayard et al, 2005; Feng et al, 2010; Shen et al, 2013)

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