Potential antiinflammatory effects of acupuncture in a chronic stress model of depression in rats

Accumulating evidence indicates that inflammation may contribute to the pathophysiology of depression. Acupuncture in traditional Chinese medicine has been considered an effective treatment for depression. However, whether the mechanisms that underlie the antidepressant effect of acupuncture are related to its antiinflammatory properties remains unclear. In the present study, rats were exposed to chronic unpredictable mild stress (CUMS) for 28 days to induce depressive-like behavior. Body weight, sucrose preference, and locomotor activity in the open field were measured. After the behavioral tests, reverse transcription polymerase chain reaction was used to determine the mRNA expression of proinflammatory cytokines (interleukin-1β [IL-1β], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF-α]), and enzyme-linked immunosorbent assay was used to detect cytokine concentrations. CUMS rats exhibited decrease in body weight, sucrose preference, and locomotor activity in the open field test. Chronic acupuncture and fluoxetine treatment reversed CUMS-induced depressive-like behavior. Compared with control rats, the mRNA and protein expression of IL-1β, IL-6, and TNF-α in the hippocampus and prefrontal cortex and cytokine concentrations in serum significantly increased in CUMS rats. Acupuncture and fluoxetine treatment significantly decreased the levels of proinflammatory cytokines in the hippocampus, prefrontal cortex, and serum. These results suggest that acupuncture has antidepressant-like effects, and its mechanism of action appears to involve the inhibition of proinflammatory cytokines.

[1]  R. Dantzer,et al.  The type 1 TNF receptor and its associated adapter protein, FAN, are required for TNFα-induced sickness behavior , 2008, Psychopharmacology.

[2]  O. Çalıyurt,et al.  Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder , 2003, Psychopharmacology.

[3]  K. Chopra,et al.  Neuropsychopharmacological effect of sesamol in unpredictable chronic mild stress model of depression: behavioral and biochemical evidences , 2011, Psychopharmacology.

[4]  Zhang-Jin Zhang,et al.  The effectiveness and safety of acupuncture therapy in depressive disorders: systematic review and meta-analysis. , 2010, Journal of affective disorders.

[5]  C. Pariante,et al.  The role of immune genes in the association between depression and inflammation: A review of recent clinical studies , 2013, Brain, Behavior, and Immunity.

[6]  E. Brietzke,et al.  Therapeutic potential of interleukin-6 antagonism in bipolar disorder. , 2011, Medical hypotheses.

[7]  V. Arolt,et al.  Clinical characteristics of inflammation-associated depression: Monocyte gene expression is age-related in major depressive disorder , 2015, Brain, Behavior, and Immunity.

[8]  Jin Yu,et al.  Glia atrophy in the hippocampus of chronic unpredictable stress-induced depression model rats is reversed by electroacupuncture treatment. , 2011, Journal of affective disorders.

[9]  Y. Tu,et al.  Acupuncture Activates ERK-CREB Pathway in Rats Exposed to Chronic Unpredictable Mild Stress , 2013, Evidence-based complementary and alternative medicine : eCAM.

[10]  B. Leonard,et al.  Imbalance between Pro- and Anti-inflammatory Cytokines, and between Th1 and Th2 Cytokines in Depressed Patients: The Effect of Electroacupuncture or Fluoxetine Treatment , 2009, Pharmacopsychiatry.

[11]  T Tabira,et al.  Chronic stress attenuates glucocorticoid negative feedback: involvement of the prefrontal cortex and hippocampus , 2003, Neuroscience.

[12]  Handi Zhang,et al.  Changes in proinflammatory cytokines and white matter in chronically stressed rats , 2015, Neuropsychiatric disease and treatment.

[13]  R. Kessler.  The costs of depression. , 2012, The Psychiatric clinics of North America.

[14]  R. Spengler,et al.  Brain-Derived Tumor Necrosis Factor-α and Its Involvement in Noradrenergic Neuron Functioning Involved in the Mechanism of Action of an Antidepressant , 2004, Journal of Pharmacology and Experimental Therapeutics.

[15]  H. Anisman,et al.  Stress, depression, and anhedonia: Caveats concerning animal models , 2005, Neuroscience & Biobehavioral Reviews.

[16]  Abraham Weizman,et al.  Evidence for an inhibitory immunomodulatory effect of selected antidepressants on rat splenocytes: possible relevance to depression and hyperactive-immune disorders. , 2008, International immunopharmacology.

[17]  Fang Wang,et al.  Acupoint specificity on acupuncture regulation of hypothalamic- pituitary-adrenal cortex axis function , 2015, BMC Complementary and Alternative Medicine.

[18]  P. Willner,et al.  Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant , 2004, Psychopharmacology.

[19]  S. Rivest,et al.  How the blood talks to the brain parenchyma and the paraventricular nucleus of the hypothalamus during systemic inflammatory and infectious stimuli. , 2000 .

[20]  G. Kenis,et al.  Effects of antidepressants on the production of cytokines. , 2002, The international journal of neuropsychopharmacology.

[21]  M. Maes,et al.  Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression , 2012, Neuroscience & Biobehavioral Reviews.

[22]  J. Suls,et al.  Associations of Depression With C-Reactive Protein, IL-1, and IL-6: A Meta-Analysis , 2009, Psychosomatic medicine.

[23]  M. Farina,et al.  Ascorbic acid treatment, similarly to fluoxetine, reverses depressive-like behavior and brain oxidative damage induced by chronic unpredictable stress. , 2012, Journal of psychiatric research.

[24]  N. Pomara,et al.  A review of the relationship between proinflammatory cytokines and major depressive disorder. , 2014, Journal of affective disorders.

[25]  S. Janelidze,et al.  Changes in behaviour and cytokine expression upon a peripheral immune challenge , 2011, Behavioural Brain Research.

[26]  M. Maes,et al.  Targeting classical IL-6 signalling or IL-6 trans-signalling in depression? , 2014, Expert opinion on therapeutic targets.

[27]  P. Mikołajczak,et al.  The influence of mianserin on TNF-α, IL-6 and IL-10 serum levels in rats under chronic mild stress , 2014, Pharmacological reports : PR.

[28]  M. Schaalan,et al.  Effects of Octreotide in Chronically Mild Stressed Rats: Possible Role of Immune and Oxidative Stress Pathways , 2011, Neurochemical Research.

[29]  John J. B. Allen,et al.  Acupuncture for depression: a randomized controlled trial. , 2006, The Journal of clinical psychiatry.

[30]  Wenzheng Zhang,et al.  Pro- and anti-inflammatory cytokines expression in rat's brain and spleen exposed to chronic mild stress: Involvement in depression , 2011, Behavioural Brain Research.

[31]  Charles L. Raison,et al.  Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression , 2009, Biological Psychiatry.

[32]  T. Postolache,,et al.  Tumor necrosis factor alpha, interleukin-1 beta, interleukin-6 and major histocompatibility complex molecules in the normal brain and after peripheral immune challenge , 2005, Neurological research.

[33]  M. Fava,et al.  A pilot study of acupuncture monotherapy in patients with major depressive disorder. , 2012, Journal of affective disorders.

[34]  M. Schwarz,et al.  Inflammatory Biomarkers and Depression , 2011, Neurotoxicity Research.

[35]  G. MacQueen,et al.  The hippocampus in major depression: evidence for the convergence of the bench and bedside in psychiatric research? , 2011, Molecular Psychiatry.

[36]  Hyejung Lee,et al.  Modulatory effects of acupuncture on murine depression-like behavior following chronic systemic inflammation , 2012, Brain Research.

[37]  V. Camus,et al.  Is unpredictable chronic mild stress (UCMS) a reliable model to study depression-induced neuroinflammation? , 2012, Behavioural Brain Research.

[38]  J. Koo,et al.  IL-1β is an essential mediator of the antineurogenic and anhedonic effects of stress , 2008, Proceedings of the National Academy of Sciences.

[39]  C. Aston,et al.  Original Research Article , 2004 .

[40]  Hi-Joon Park,et al.  Acupuncture increases neuropeptide Y expression in hippocampus of maternally-separated rats , 2003, Neuroscience Letters.

[41]  F. Luo,et al.  Chronic treatment with celecoxib reverses chronic unpredictable stress-induced depressive-like behavior via reducing cyclooxygenase-2 expression in rat brain. , 2009, European journal of pharmacology.

[42]  Yong-Ku Kim,et al.  The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression , 2016, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[43]  R. Dantzer,et al.  Cytokines, stress, and depression. Conclusions and perspectives. , 1999, Advances in experimental medicine and biology.