Bax inhibitor-1 overexpression in prelimbic cortex protects rats against depression-like behavior induced by olfactory bulbectomy and reduces apoptotic and inflammatory signals

ABSTRACT Background and purpose: Depression is a mental disorder characterized by a pervasive low mood and loss of pleasure or interest in usual activities, and often results in the impairment of learning and memory. Bax inhibitor-1 (BI-1) has been reported to be involved in the pathological mechanisms for neurodegenerative disorders including depression. Here, we aimed to investigate the role of BI-1 in regulating depression-like behavior induced by olfactory bulbectomy (OB) in rats and the possible mechanism. Methods: Adeno-associated virus vectors expressing BI-1 (AAV-BI-1) were bilaterally microinjected into the prelimbic cortex (PFC-PL) to establish a BI-1 overexpression model in the PFC-PL of rats. TUNEL staining was used to evaluate the cellular apoptosis rate in the PFC-PL. Western blot analysis was performed to examine the expressions of apoptotic and inflammatory signals. Results: BI-1 overexpression significantly attenuated the OB-induced behavioral abnormalities, including the decreased hyperactivity in the open field, decreased immobility time in the forced swimming test, as well as the increased sucrose consumption. BI-1 overexpression significantly inhibited cellular apoptosis in the PFC-PL of OB rats. The expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, B-cell lymphoma (Bcl)-2 associated X protein (Bax), and caspase-3 in the PFC-PL of OB rats were significantly increased as compared with the sham rats, but the Bcl-2 and IL-10 expressions were decreased, whereas BI-1 overexpression significantly suppressed the changes of these proteins in the PFC-PL of OB rats. Conclusion: These results indicated that BI-1 may play an anti-depression function with concurrent regulation of apoptotic and inflammatory signals.

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

[2]  Y. Chai,et al.  Pharmacokinetic comparison of seven major bioactive components in normal and depression model rats after oral administration of Baihe Zhimu decoction by liquid chromatography–tandem mass spectrometry , 2018, Journal of pharmaceutical and biomedical analysis.

[3]  Young-Chul Chung,et al.  Effects of Chronic Mild Stress in Female Bax Inhibitor-1-Gene Knockout Mice , 2012, Clinical Psychopharmacology and Neuroscience.

[4]  B. Czéh,et al.  Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: Implications for depression and antidepressant action , 2010, European Neuropsychopharmacology.

[5]  M. Irwin,et al.  Inflammatory Markers and Sleep Disturbance in Major Depression , 2005, Psychosomatic medicine.

[6]  Hao Wang,et al.  Venlafaxine inhibits apoptosis of hippocampal neurons by up-regulating brain-derived neurotrophic factor in a rat depression model. , 2014, Die Pharmazie.

[7]  I. Bezprozvanny,et al.  The C Terminus of Bax Inhibitor-1 Forms a Ca2+-permeable Channel Pore* , 2011, The Journal of Biological Chemistry.

[8]  John Calvin Reed,et al.  Bax inhibitor-1, a mammalian apoptosis suppressor identified by functional screening in yeast. , 1998, Molecular cell.

[9]  A. Zangen,et al.  Knockdown of brain-derived neurotrophic factor in specific brain sites precipitates behaviors associated with depression and reduces neurogenesis , 2009, Molecular Psychiatry.

[10]  R. Godbout,et al.  Behavioural signs of depression and apoptosis in the limbic system following myocardial infarction: effects of sertraline , 2009, Journal of psychopharmacology.

[11]  Rongjuan Guo,et al.  Effect of XingPiJieYu decoction on spatial learning and memory and cAMP-PKA-CREB-BDNF pathway in rat model of depression through chronic unpredictable stress , 2017, BMC Complementary and Alternative Medicine.

[12]  S. Lipton,et al.  BI-1 regulates an apoptosis pathway linked to endoplasmic reticulum stress. , 2004, Molecular cell.

[13]  V. Zakuth,et al.  Increased apoptosis in patients with major depression: A preliminary study. , 1999, Journal of immunology.

[14]  C. Nemeroff.  The burden of severe depression: a review of diagnostic challenges and treatment alternatives. , 2007, Journal of psychiatric research.

[15]  E. Zorrilla,et al.  The Relationship of Depression and Stressors to Immunological Assays: A Meta-Analytic Review , 2001, Brain, Behavior, and Immunity.

[16]  M. Filip,et al.  Oxidative stress as an etiological factor and a potential treatment target of psychiatric disorders. Part 1. Chemical aspects and biological sources of oxidative stress in the brain , 2015, Pharmacological reports : PR.

[17]  Andrew H. Miller,et al.  Cytokines sing the blues: inflammation and the pathogenesis of depression. , 2006, Trends in immunology.

[18]  M. Albitar,et al.  Cognitive impairment, fatigue, and cytokine levels in patients with acute myelogenous leukemia or myelodysplastic syndrome , 2005, Cancer.

[19]  G. Simutkin,et al.  Signs of apoptosis of immunocompetent cells in patients with depression , 2007, Neuroscience and Behavioral Physiology.

[20]  T. Pollmächer,et al.  Cytokine-associated emotional and cognitive disturbances in humans. , 2001, Archives of general psychiatry.

[21]  A. Ehlis,et al.  Consensus paper of the WFSBP Task Force on Biological Markers: Biological Markers in Depression , 2007, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[22]  D. Charney,et al.  Noradrenergic and serotonergic receptor system function in panic disorder and depression , 1988, Acta psychiatrica Scandinavica. Supplementum.

[23]  A. Serretti,et al.  Possible association between –G308A tumour necrosis factor-&agr; gene polymorphism and major depressive disorder in the Korean population , 2003, Psychiatric genetics.

[24]  M. Maes,et al.  Major depression and activation of the inflammatory response system. , 1999, Advances in experimental medicine and biology.

[25]  M. Filip,et al.  Oxidative stress as an etiological factor and a potential treatment target of psychiatric disorders. Part 2. Depression, anxiety, schizophrenia and autism , 2015, Pharmacological reports : PR.

[26]  S. Patten.  Major Depression Prevalence is Very High, but the Syndrome is a Poor Proxy for Community Populations' Clinical Treatment Needs , 2008, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[27]  R. Yadav,et al.  The characteristics of Bax inhibitor-1 and its related diseases. , 2014, Current molecular medicine.

[28]  Y. Mao,et al.  Effects of Electroacupuncture at Governor Vessel Acupoints on Neurotrophin-3 in Rats with Experimental Spinal Cord Injury , 2016, Neural plasticity.

[29]  A. Serretti,et al.  Depressive syndrome in major psychoses: a study on 1351 subjects , 2004, Psychiatry Research.

[30]  Xue-jun Li,et al.  Antidepressant effects of curcumin in the forced swim test and olfactory bulbectomy models of depression in rats , 2005, Pharmacology Biochemistry and Behavior.

[31]  H. Critchley,et al.  Peripheral Inflammation is Associated with Altered Substantia Nigra Activity and Psychomotor Slowing in Humans , 2008, Biological Psychiatry.

[32]  M Aschner,et al.  ALTERED EXPRESSION OF GENES INVOLVED IN INFLAMMATION AND APOPTOSIS IN FRONTAL CORTEX IN MAJOR DEPRESSION , 2010, Molecular Psychiatry.

[33]  J. Grafman.  The Structured Event Complex and the Human Prefrontal Cortex , 2009 .

[34]  John Calvin Reed,et al.  Cytoprotective gene bi-1 is required for intrinsic protection from endoplasmic reticulum stress and ischemia-reperfusion injury. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Nicholas B. Allen,et al.  The emergence of depression in adolescence: Development of the prefrontal cortex and the representation of reward , 2008, Neuroscience & Biobehavioral Reviews.

[36]  M. Filip,et al.  Changes in the Brain Endocannabinoid System in Rat Models of Depression , 2017, Neurotoxicity Research.

[37]  J. Jahng,et al.  Increased depression-like behaviors with dysfunctions in the stress axis and the reward center by free access to highly palatable food , 2014, Neuroscience.

[38]  T. Kamarck,et al.  A prospective evaluation of the directionality of the depression–inflammation relationship , 2009, Brain, Behavior, and Immunity.

[39]  Je-Yong Choi,et al.  An acidic pH environment increases cell death and pro-inflammatory cytokine release in osteoblasts: the involvement of BAX inhibitor-1. , 2011, The international journal of biochemistry & cell biology.

[40]  E. Stenman,et al.  Increased monoaminergic neurotransmission improves compliance with physical activity recommendations in depressed patients with fatigue. , 2013, Medical hypotheses.

[41]  O. Wolkowitz,et al.  Low serum IL-10 concentrations and loss of regulatory association between IL-6 and IL-10 in adults with major depression. , 2009, Journal of psychiatric research.

[42]  S. Tsai,et al.  Association Study of the Interleukin-1beta (C-511T) Genetic Polymorphism with Major Depressive Disorder, Associated Symptomatology, and Antidepressant Response , 2003, Neuropsychopharmacology.

[43]  Antidepressant-like activity of magnesium in the olfactory bulbectomy model is associated with the AMPA/BDNF pathway , 2014, Psychopharmacology.

[44]  P. Xie,et al.  Increased apoptosis and different regulation of pro-apoptosis protein bax and anti-apoptosis protein bcl-2 in the olfactory bulb of a rat model of depression , 2011, Neuroscience Letters.