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

Abstract

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).

Exercise modulates central and peripheral inflammatory responses and ameliorates methamphetamine-induced anxiety-like symptoms in mice

“…It has not been reported that treadmill exercise can improve anxiety-like symptoms in METH acute withdrawal by counteracting the central inflammation induced by METH. Consistent with the results of a previous clinical study ( Yang J. et al, 2020 ), our behavioral results demonstrated that moderate-intensity treadmill exercise can alleviate anxiety-like symptoms during acute METH withdrawal in mice. Numerous studies in related fields have shown that exercise can regulate microglial activation and the inflammatory response in neurodegenerative diseases, such as Alzheimer’s disease ( Lu et al, 2017 ).…”

Aerobic exercise as a promising nonpharmacological therapy for the treatment of substance use disorders

“…exercise training regime improved their aerobic capacity, muscle strength, endurance, and percentage of body fat, all of which correlates with reduction of depression symptoms (Dolezal et al, 2013;Haglund et al, 2015). Studies by Haglund et al (2015), Rawson et al (2015), and Yang et al (2020) showed that exercise also attenuates METH-induced depression and anxiety symptoms in early recovery and METH-abstinent individuals. Also, exercise improves the quality of life of METH users (as measured by questionnaires) through enhancement of psychological health, as well as their social relationships (Muller & Clausen, 2015).…”

“…For example, exercise reduces METH‐induced deficits on dopamine receptors 1 and 3 in the striatal area, both of which are important in the reward system (Robertson et al., 2016). Another study showed that exercise counteracts METH withdrawal‐induced increases in BDNF plasma levels, and TrkB mRNA in peripheral blood mononuclear cells, which correlates with attenuation of depression and anxiety behavior (Yang et al., 2020). In addition, functional magnetic resonance neuroimaging studies showed that the efficiency and direction of information transmission between left and right prefrontal cortices, and/or left and right motor cortices were lower in female subjects with METH dependencies in training (practicing kickboxing exercise) and resting states, compared with control groups.…”

“…(2015), and Yang et al. (2020) showed that exercise also attenuates METH‐induced depression and anxiety symptoms in early recovery and METH‐abstinent individuals. Also, exercise improves the quality of life of METH users (as measured by questionnaires) through enhancement of psychological health, as well as their social relationships (Muller & Clausen, 2015).…”

Potential Effects of Nrf2 in Exercise Intervention of Neurotoxicity Caused by Methamphetamine Oxidative Stress

“…Using functional near-infrared spectroscopy (fNIRS) and heart rate signal evaluation, researchers found that physical training can affect brain functional connectivity in METH-dependent subjects to a certain extent [ 87 , 88 ]. Recent studies have further demonstrated that exercise can reduce depression and anxiety during withdrawal in patients with long-term METH exposure, possibly through mechanisms related to plasma BDNF and TrkB levels in peripheral blood mononuclear cells [ 89 ].…”