Dihydromyricetin Alleviates Diabetic Neuropathic Pain and Depression Comorbidity Symptoms by Inhibiting P2X7 Receptor.
Journal: 2019/November - Frontiers in Psychiatry
ISSN: 1664-0640
Abstract:
Diabetic neuropathic pain (DNP) and major depressive disorder (MDD) are common complications of diabetes mellitus and mutually affect each other. As a member of the ATP-gated ion channel family, P2X7 receptor is associated with the transduction of pain signal and the onset of depression. The aim of this study was to investigate the effects of dihydromyricetin (DHM) on rats with comorbid DNP and MDD. After the comorbid model was established, rat behavior changes were monitored by measuring the mechanical withdrawal threshold, thermal withdrawal latency, sugar water preference, immobility time in the forced-swim test, and open-field test parameters. The expressions of P2X7 receptor in the dorsal root ganglia (DRGs), spinal cord, and hippocampus were assessed by quantitative real-time PCR, Western blotting, and double immunofluorescence. We found that hyperalgesia, allodynia, and depressive behaviors of rats with comorbid DNP and MDD were relieved by treatment with DHM or application of a short-hairpin RNA for P2X7 receptor. The expression levels of P2X7, phosphorylated extracellular signal-regulated kinase 1/2, tumor necrosis factor α, and interleukin 1ß were increased in the DRGs, spinal cord, and hippocampus of rats in the model group but restored after DHM or P2X7 short-hairpin RNA treatment. In conclusion, P2X7 receptor in the DRGs, spinal cord, and hippocampus participates in the transduction of DNP and MDD signals. DHM seems to relieve comorbid DNP and MDD by reducing the expression of P2X7 receptor in the DRGs, spinal cord, and hippocampus and may be an effective new drug for the treatment of patients with both DNP and MDD.
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Front Psychiatry 10: 770

Dihydromyricetin Alleviates Diabetic Neuropathic Pain and Depression Comorbidity Symptoms by Inhibiting P2X<sub>7</sub> Receptor

Department of Physiology, Basic Medical College, Nanchang University, Nanchang, China
Sport Biological Centre, China Institute of Sport Science, Beijing, China
Department of Preventive Dentistry, Affiliated Stomatological Hospital of Nanchang University, Nanchang, China
Basic Medical College of Grade 2017, Nanchang University, Nanchang, China
Jiangxi Provincial Key Laboratory of Autonomic Nervous Function and Disease, Nanchang University, Nanchang, China
Edited by: James Alan Bourgeois, Baylor Scott and White Health, United States
Reviewed by: Yong Tang, Chengdu University of Traditional Chinese Medicine, China; Chamindi Seneviratne, University of Maryland, Baltimore, United States
*Correspondence: Yun Gao, nc.ude.ucn@nuyoag
This article was submitted to Mood and Anxiety Disorders, a section of the journal Frontiers in Psychiatry
Edited by: James Alan Bourgeois, Baylor Scott and White Health, United States
Reviewed by: Yong Tang, Chengdu University of Traditional Chinese Medicine, China; Chamindi Seneviratne, University of Maryland, Baltimore, United States
Received 2018 Sep 13; Accepted 2019 Sep 24.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Abstract

Diabetic neuropathic pain (DNP) and major depressive disorder (MDD) are common complications of diabetes mellitus and mutually affect each other. As a member of the ATP-gated ion channel family, P2X7 receptor is associated with the transduction of pain signal and the onset of depression. The aim of this study was to investigate the effects of dihydromyricetin (DHM) on rats with comorbid DNP and MDD. After the comorbid model was established, rat behavior changes were monitored by measuring the mechanical withdrawal threshold, thermal withdrawal latency, sugar water preference, immobility time in the forced-swim test, and open-field test parameters. The expressions of P2X7 receptor in the dorsal root ganglia (DRGs), spinal cord, and hippocampus were assessed by quantitative real-time PCR, Western blotting, and double immunofluorescence. We found that hyperalgesia, allodynia, and depressive behaviors of rats with comorbid DNP and MDD were relieved by treatment with DHM or application of a short-hairpin RNA for P2X7 receptor. The expression levels of P2X7, phosphorylated extracellular signal–regulated kinase 1/2, tumor necrosis factor α, and interleukin 1ß were increased in the DRGs, spinal cord, and hippocampus of rats in the model group but restored after DHM or P2X7 short-hairpin RNA treatment. In conclusion, P2X7 receptor in the DRGs, spinal cord, and hippocampus participates in the transduction of DNP and MDD signals. DHM seems to relieve comorbid DNP and MDD by reducing the expression of P2X7 receptor in the DRGs, spinal cord, and hippocampus and may be an effective new drug for the treatment of patients with both DNP and MDD.

Keywords: dihydromyricetin, P2X7 receptor, diabetic neuropathic pain, major depressive disorder, dorsal root ganglion, spinal cord, hippocampus
Abstract

Acknowledgments

We thank Prof. Shangdong Liang and Prof Guodong Li for assisting us in the experimental design.

Acknowledgments

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