Electroacupuncture ameliorates post-traumatic stress disorder in rats via a mechanism involving the BDNF-TrkB signaling pathway

Mi Li; Yiqiang Xie; Kun Niu; Kai Li

doi:10.14715/cmb/2020.66.3.26

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Vol. 66 No. 3: Issue 3

Issue Published : June 8, 2020

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Electroacupuncture ameliorates post-traumatic stress disorder in rats via a mechanism involving the BDNF-TrkB signaling pathway

https://doi.org/10.14715/cmb/2020.66.3.26

Mi Li

Chinese medicine College, Hainan Medical University, No.3, Xueyuan Road, Longhua District, Haikou City, Hainan Province, China

Yiqiang Xie

Chinese medicine College, Hainan Medical University, No.3, Xueyuan Road, Longhua District, Haikou City, Hainan Province, China

Kun Niu

Chinese medicine College, Hainan Medical University, No.3, Xueyuan Road, Longhua District, Haikou City, Hainan Province, China

Kai Li

Chinese medicine College, Hainan Medical University, No.3, Xueyuan Road, Longhua District, Haikou City, Hainan Province, China

Corresponding Author(s) : Yiqiang Xie

scnpi9@163.com

Cellular and Molecular Biology, Vol. 66 No. 3: Issue 3
Article Published : June 5, 2020

Abstract

Post-traumatic stress disorder (PTSD) is a mental health condition triggered by a terrifying event, causing flashbacks, nightmares and severe anxiety. It develops in individuals who have experienced a shocking, scary, or dangerous event. Electroacupuncture is reported to be effective for the treatment of PTSD. The present study was carried out to investigate the protective effect of electroacupuncture in a rat model of PTSD, and the mechanism involved. Specific-pathogen-free male Sprague Dawley rats (n = 30) weighing 180 – 220 g (mean weight = 200 ± 20 g) were randomly assigned to three groups of ten rats each: control group, single-prolonged stress (SPS) group, and treatment group. The treatment group rats received electroacupuncture. Changes in PTSD-like behavior were assessed using locomotor activity, elevated plus-maze (EPM) and fear conditioning tests. The mRNA and protein expressions of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) were determined using real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Co-immunoprecipitation (Co-IP) was used to measure BDNF and TrkB binding interaction, while chromatin immunoprecipitation (ChIP) was used to evaluate the binding between cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) and its target genes. Electroacupuncture significantly increased locomotor activity and exploratory behavior, but significantly reduced general fear and anxiety in SPS rats (p < 0.05). It also significantly upregulated the mRNA and protein expressions of BDNF and TrkB, and increased the binding of BDNF to its receptor TrkB (p < 0.05). Electroacupuncture significantly increased the binding of CREB to BDNF promoter region (p < 0.05). Electroacupuncture ameliorates PTSD in rats via a mechanism involving the BDNF-TrkB signaling pathway.

Keywords

Brain-derived neurotrophic factor Electroacupuncture Post-traumatic stress disorder Single-prolonged stress Tropomyosin receptor kinase B.

Li, M., Xie, Y., Niu, K., & Li, K. (2020). Electroacupuncture ameliorates post-traumatic stress disorder in rats via a mechanism involving the BDNF-TrkB signaling pathway. Cellular and Molecular Biology, 66(3), 165–170. https://doi.org/10.14715/cmb/2020.66.3.26

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References

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Zhao ZT, Zhao YD, Zheng QH, Yan XK. Advances in modern clinical research on acupuncture intervention for PTSD. Lishizhen Med Mater Med Res 2015; 26: 1444-1446.
Hollifield M, Sinclair-Lian N, Warner TD, Hammerschlag R. Acupuncture for posttraumatic stress disorder: a randomized controlled pilot trial. J Nerv Ment Dis 2007; 195: 504-513.
Zhang H, Yuan CF, Ran LH, Yuan Q, Yuan XL, Hu YP, et al. Randomized-controlled clinical trial of different acupuncture therapies in treating posttraumatic stress disorder after 5.12 Wenchuan Earthquake. Chin J Tradit Chin Med Pharm 2010; 25: 1505-1510.
Li M, Li K, Zhang H. Study on the mechanism of TMRK electroacupuncture in repairing synaptic plasticity in amygdala and hippocampus to relieve fear memory in PTSD rats. Technol Health Care 2019; 27: 425-443.
Yagasaki Y, Numakawa T, Kumamaru E. Chronic antidepressants potentiate via sigma-1 receptors the brain-derived neurotrophic factor-induced signaling for glutamate release. J Biol Chem 2006; 281: 12941-12949.
Li Y. Role and Mechanism of BDNF Regulation and Its Receptor Signals in Memory and Emotional Related Behaviors. Shan Dong University 2018.
Zhang JC, Yao W, Hashimoto K. Brain-derived Neurotrophic Factor (BDNF)-TrkB Signaling in Inflammation-related Depression and Potential Therapeutic Targets. Curr Neuropharmacol 2016; 14: 721-731.
Koike H, Fukumoto K, Iijima M, Chaki S. Role of BDNF/TrkB signaling in antidepressant-like effects of a group II metabotropic glutamate receptor antagonist in animal models of depression. Behav Brain Res 2013; 238: 48-52.
Hauck S, Kapczinski F, Roesler R, de Moura Silveira E Jr, Magalhí£es PV, Kruel LR, et al. Serum brain-derived neurotrophic factor in patients with trauma psychopathology. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 459-462.
Green CR, Corsi-Travali S, Neumeister A. The Role of BDNF-TrkB Signaling in the Pathogenesis of PTSD. J Depress Anxiety 2013; 2013: 1.
Noble LJ, Gonzalez IJ, Meruva VB, Callahan KA, Belfort BD, Ramanathan KR, et al. Effects of vagus nerve stimulation on extinction of conditioned fear and post-traumatic stress disorder symptoms in rats. Transl Psychiatry 2017; 7: 1217.
Nelson JD, Denisenko O, Bomsztyk K. Protocol for the fast chromatin immunoprecipitation (ChIP) method. Nat Protoc 2006; 1: 179-185.
Frank SR, Schroeder M, Fernandez P, Taubert S, Amati B. Binding of c-Myc to chromatin mediates mitogen-induced acetylation of histone H4 and gene activation. Genes Dev 2001; 15: 2069-2082.
Careaga M, Girardi C, Suchecki D. Understanding posttraumatic stress disorder through fear conditioning, extinction and reconsolidation. Neurosci Biobehav Rev 2016; 71: 48-57.
Andero R, Ressler KJ. Fear extinction and BDNF: translating animal models of PTSD to the clinic. Genes Brain Behav 2012; 11: 503-512.
Andero R, Daviu N, Escorihuela RM, Nadal R, Armario A. 7,8-dihydroxyflavone, a TrkB receptor agonist, blocks long-term spatial memory impairment caused by immobilization stress in rats. Hippocampus 2012; 22: 399-408.
Baker-Andresen D, Flavell CR, Li X, Bredy TW. Activation of BDNF signaling prevents the return of fear in female mice. Learn Mem 2013; 20: 237-240.
Tural íœ, Aker AT, í–nder E, Sodan HT, íœnver H, Akansel G. Neurotrophic factors and hippocampal activity in PTSD. PLoS One 2018; 13: 197889.
Hong C, Efferth T. Systematic Review on Post-Traumatic Stress Disorder Among Survivors of the Wenchuan Earthquake. Trauma Violence Abuse 2016; 17: 542-561.

References

First MB. Diagnostic and statistical manual of mental disorders and clinical utility. J Nerv Ment Dis 2013; 201: 727-729.

Breslau N, Kessler RC. The stressor criterion in DSM-IV posttraumatic stress disorder: an empirical investigation. Biol Psychiatry 2001; 50: 699-704.

Cook JM, Dinnen S, Simiola V, Thompson R, Schnurr PP. VA Residential Provider Perceptions of Dissuading Factors to the Use of Two Evidence-Based PTSD Treatments. Prof Psychol Res Pr 2014; 45: 136-142.

Guo J, Wu P, Tian D, Wang X, Zhang W, Zhang X, et al. Post-traumatic stress disorder among adult survivors of the Wenchuan earthquake in China: a repeated cross-sectional study. J Anxiety Disord 2014; 28: 75-82.

Kim YD, Heo I, Shin BC, Crawford C, Kang HW, Lim JH. Acupuncture for posttraumatic stress disorder: a systematic review of randomized controlled trials and prospective clinical trials. Evid Based Complement Alternat Med 2013; 2013: 615857.

Zhao ZT, Zhao YD, Zheng QH, Yan XK. Advances in modern clinical research on acupuncture intervention for PTSD. Lishizhen Med Mater Med Res 2015; 26: 1444-1446.

Hollifield M, Sinclair-Lian N, Warner TD, Hammerschlag R. Acupuncture for posttraumatic stress disorder: a randomized controlled pilot trial. J Nerv Ment Dis 2007; 195: 504-513.

Zhang H, Yuan CF, Ran LH, Yuan Q, Yuan XL, Hu YP, et al. Randomized-controlled clinical trial of different acupuncture therapies in treating posttraumatic stress disorder after 5.12 Wenchuan Earthquake. Chin J Tradit Chin Med Pharm 2010; 25: 1505-1510.

Li M, Li K, Zhang H. Study on the mechanism of TMRK electroacupuncture in repairing synaptic plasticity in amygdala and hippocampus to relieve fear memory in PTSD rats. Technol Health Care 2019; 27: 425-443.

Yagasaki Y, Numakawa T, Kumamaru E. Chronic antidepressants potentiate via sigma-1 receptors the brain-derived neurotrophic factor-induced signaling for glutamate release. J Biol Chem 2006; 281: 12941-12949.

Li Y. Role and Mechanism of BDNF Regulation and Its Receptor Signals in Memory and Emotional Related Behaviors. Shan Dong University 2018.

Zhang JC, Yao W, Hashimoto K. Brain-derived Neurotrophic Factor (BDNF)-TrkB Signaling in Inflammation-related Depression and Potential Therapeutic Targets. Curr Neuropharmacol 2016; 14: 721-731.

Koike H, Fukumoto K, Iijima M, Chaki S. Role of BDNF/TrkB signaling in antidepressant-like effects of a group II metabotropic glutamate receptor antagonist in animal models of depression. Behav Brain Res 2013; 238: 48-52.

Hauck S, Kapczinski F, Roesler R, de Moura Silveira E Jr, Magalhí£es PV, Kruel LR, et al. Serum brain-derived neurotrophic factor in patients with trauma psychopathology. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 459-462.

Green CR, Corsi-Travali S, Neumeister A. The Role of BDNF-TrkB Signaling in the Pathogenesis of PTSD. J Depress Anxiety 2013; 2013: 1.

Noble LJ, Gonzalez IJ, Meruva VB, Callahan KA, Belfort BD, Ramanathan KR, et al. Effects of vagus nerve stimulation on extinction of conditioned fear and post-traumatic stress disorder symptoms in rats. Transl Psychiatry 2017; 7: 1217.

Nelson JD, Denisenko O, Bomsztyk K. Protocol for the fast chromatin immunoprecipitation (ChIP) method. Nat Protoc 2006; 1: 179-185.

Frank SR, Schroeder M, Fernandez P, Taubert S, Amati B. Binding of c-Myc to chromatin mediates mitogen-induced acetylation of histone H4 and gene activation. Genes Dev 2001; 15: 2069-2082.

Careaga M, Girardi C, Suchecki D. Understanding posttraumatic stress disorder through fear conditioning, extinction and reconsolidation. Neurosci Biobehav Rev 2016; 71: 48-57.

Andero R, Ressler KJ. Fear extinction and BDNF: translating animal models of PTSD to the clinic. Genes Brain Behav 2012; 11: 503-512.

Andero R, Daviu N, Escorihuela RM, Nadal R, Armario A. 7,8-dihydroxyflavone, a TrkB receptor agonist, blocks long-term spatial memory impairment caused by immobilization stress in rats. Hippocampus 2012; 22: 399-408.

Baker-Andresen D, Flavell CR, Li X, Bredy TW. Activation of BDNF signaling prevents the return of fear in female mice. Learn Mem 2013; 20: 237-240.

Tural íœ, Aker AT, í–nder E, Sodan HT, íœnver H, Akansel G. Neurotrophic factors and hippocampal activity in PTSD. PLoS One 2018; 13: 197889.

Hong C, Efferth T. Systematic Review on Post-Traumatic Stress Disorder Among Survivors of the Wenchuan Earthquake. Trauma Violence Abuse 2016; 17: 542-561.

Author biographies is not available.