Dr. Jun-Feng Wang

Associate Professor

Department of Pharmacology and Therapeutics

University of Manitoba

Email: jun-feng.wang@med.umanitoba.ca

Research Focus:

The primary goal of my research is to understand the role of oxidative stress-induced damage to neurotransmission in bipolar disorder; and to understand the neuroprotective mechanism of mood stabilizing drugs against oxidative stress. These studies should lead to identifying new therapeutic targets for investigation in clinical trials in the near future, contributing to new and more effective therapies for bipolar disorder with fewer side effects.

Manic-depressive bipolar disorder affects approximately 1.5% of the population and is characterized by episodes of mania and depression with significant morbidity and mortality. Increasing evidence indicates that mitochondrial dysfunction is associated with bipolar disorder. Mitochondrial dysfunction is the major source for production of reactive oxygen species (ROS) that cause oxidative stress.  Since mitochondria are enriched in the synaptic terminals, dysfunctional mitochondria may increase ROS production, resulting in oxidative modification of synaptic proteins which further interrupts neurotransmission. We are examining how various oxidative modifications affect synaptic proteins, causing their functional change, and establishing whether oxidative modification of these synaptic proteins is associated with bipolar disorder. 

Previously, we found that mood stabilizing drugs prevent oxidative damage and up-regulate the glutathione S-transferase (GST) detoxification pathway. In order to understand the role of GST pathway in the pharmacological treatment of mood stabilizing drugs, we are currently studying if GST mediates the neuroprotective effects of mood stabilizing drugs against oxidative damage. We are examining the role of transcription factor Nrf2 transcription factor in GST pathway regulated by mood stabilizing drugs and determining role of GST pathway in mood stabilizing treatment using animal models for depression and mania.

Research techniques employed in my work include cell culturing, measurement of lipid peroxidation and protein oxidation, TUNEL staining, real time-PCR, DNA cloning, in vitro transcription and translation, cell transfection, immunoblotting analysis, co-immunoprecipitation, immunohistochemistry, electrophoretic mobility shift assay and various animal behavioural tests, among others.

Selected Recent Publications:

1.         Tan H, Shao L, Li HY, Young LT, Honer WG, Wang JF (2011). Mood stabilizer lithium prevents amphetamine-increased adductions of 4-hydroxynonenal with presynaptic proteins in rat frontal cortex. Int J Neuropsychopharmacol. Sept. 23:1-11.

2.         Andreazza AC, Shao L, Wang JF and Young LT (2010). Decreased mitochondrial complex I activity and increased oxidative damage to mitochondrial proteins in the prefrontal cortex of patients with bipolar disorder. Archives of General Psychiatry, 67: 360-8.

3.         Wang JF, Shao L, Sun X and Young LT (2009). Increased oxidative stress in anterior cingulate cortex of subjects with bipolar disorder and schizophrenia. Bipolar disorders, 11: 523-529

4.         Shao L, Cui J, Young LT and Wang JF (2008). The effect of mood stabilizer lithium on expression and activity of glutathione-S-transferase isoenzymes. Neuroscience, 151: 518-24.

5.         Wang JF (2007). Defects of mitochondrial electron transport chain in bipolar disorder: implications for mood stabilizing treatment. Canadian Journal of Psychiatry,52: 753-62. (Review)

6.         Cui J, Shao L, Young LT and Wang JF (2007). Role of glutathione in neuroprotective effects of mood stabilizing drugs lithium and valproate. Neuroscience, 144: 1447-53.

7.         Shao L, Sun X, Xu L, Young LT and Wang JF (2006). Mood stabilizing drug lithium increases expression of endoplasmic reticulum stress proteins in primary cultured rat cerebralcortical cells. Life Science, 78: 1317-23.

8.         Sun X, Wang JF, Tseng M and Young LT (2006). Down regulation in components of mitochondrial electron transport chain in post-mortem frontal cortex from subjects with bipolar disorder. Journal of Psychiatry and Neuroscience, 31: 189-96.

9.         Shao L, Young LT and Wang JF (2005). Chronic treatment with mood stabilizers lithium and valproate prevents excitotoxicity by inhibiting oxidative stress in rat cerebral cortical cells. Biological Psychiatry, 58: 879-84.

10.     Wang JF, Shao L, Sun X, Young LT (2004). Glutathione S-transferase is a novel target for mood stabilizing drugs in primary cultured neurons. Journal of Neurochemistry. 88: 1477-84.