Views
11 months ago

2018 Scientific Report

  • Text
  • Institute
  • Biology
  • Methylation
  • Molecular
  • Mechanisms
  • Epigenetic
  • Michigan
  • Vari
  • Scientific

Center for

Center for Neurodegenerative Science LENA BRUNDIN, M.D., Ph.D. Dr. Brundin earned her Ph.D. in neurobiology and her M.D. from Lund University, Sweden. She joined VARI in 2012 and is an Associate Professor. RESEARCH INTERESTS We hypothesize that inflammation in the brain causes psychiatric symptoms such as depression and thoughts of suicide, and we study how inflammation can damage nerve cells and be involved in neurological conditions such as Parkinson’s disease. We are conducting clinical studies on patients in the Grand Rapids area and translational experiments in the laboratory at VARI, trying to understand the mechanisms by which inflammation affects the brain. STAFF Elena Bryleva, Ph.D. Nils Eastburg, B.S. Emily Glidden, B.S. Stan Krzyzanowski, B.A. Keerthi Rajamani, Ph.D. Infections may play a role in triggering inflammation and subsequent symptoms in patients. In collaboration with Pine Rest Christian Mental Health, we are assessing the role of herpes simplex virus infection in triggering psychiatric symptoms. Our hypothesis is that patients with depression are more vulnerable to developing mood symptoms upon reactivation of HSV infection and that the infection could trigger depressive episodes. We have found that infection with the parasite Toxoplasma gondii is associated with a sevenfold risk of attempted suicide. Some 10-20% of all Americans are infected with this parasite, which may cause subtle behavioral changes, perhaps due to low-grade chronic brain inflammation. Toxoplasma infection may be treatable using current medications, but clinical trials are needed to prove that such treatment has a beneficial effect on depressive and suicidal behavior. STUDENT Sarah Keaton, M.S. We are conducting a study of perinatal depression together with Pine Rest Christian Mental Health, Spectrum Health, and Michigan State University. This NIH-funded effort, led by Dr. Brundin, investigates the role of placental inflammation in the development of perinatal depression. The goals of the study are to understand the cause of depression during pregnancy and to find biomarkers to identify women who are at risk for such depression. We have successfully enrolled 199 women and evaluated them in pregnancy and post partum over the past three years, and we are now analyzing the data. We have identified an enzyme, aminocarboxymuconate semialdehyde decarboxylase (ACMSD), that may regulate the vulnerability to developing psychiatric and neurological symptoms upon infection or inflammation. A person having low activity of ACMSD might have difficulties in controlling inflammation. The by-products of inflammation may cause nerve cell damage and neurological and psychiatric symptoms. We are studying whether increased amounts of ACMSD can be protective and prevent symptoms of Parkinson’s disease and depression. 38 | VAN ANDEL RESEARCH INSTITUTE SCIENTIFIC REPORT

PATRIK BRUNDIN, M.D., Ph.D. Dr. Brundin earned his M.D. and Ph.D. at Lund University, Sweden. He was a professor of neuroscience at Lund before becoming a Professor and Associate Research Director of VARI in 2012. RESEARCH INTERESTS Our research mission is to understand why Parkinson’s disease (PD) develops. We use cellular and animal PD models to discover new treatments that we hope can slow disease progression. STAFF Kim Cousineau, M.P.A. Sonia George, Ph.D. Lindsay Meyerdirk, M.S. Wouter Peelaerts, Ph.D. Emmanuel Quansah, Ph.D. Keerthi Rajamani, Ph.D. Nolwen Rey, Ph.D. Emily Schulz, B.S. Jennifer Steiner, Ph.D. Misfolded variants of the protein α-synuclein (α-syn) are a main constituent of intraneuronal Lewy bodies, the protein aggregates that are the major neuropathological hallmark of PD. The mechanisms underlying α-syn pathology are poorly understood. We were one of the first groups to propose that abnormal α-syn might propagate between neurons and drive the progression of symptoms. Our interests include understanding how α-syn aggregation is triggered, how the aggregates spread, and how they cause neurological deficits. We have created a mouse model of the human disease based on injections of misfolded α-syn into the olfactory bulb. The loss of olfaction is an early change in PD, often preceding the onset of the classic motor symptoms. In our model, α-syn aggregate pathology gradually spreads along olfactory pathways, causing progressive olfactory deficits. We are now defining whether the deficits are due to neuronal death or to dysfunction in neurons that contain aggregates. The olfactory bulb model has been proposed to be a starting point of Lewy body pathology, but the initial trigger is unknown. We are currently exploring whether airborne environmental pollutants or other proinflammatory stimuli can cause α-syn aggregate pathology in the olfactory bulb. We are also examining immunotherapy and repurposed antidiabetic drugs for effects that reduce PD pathology in animal models. Given the favorable safety profile of antidiabetic agents, several are already being tested in PD clinical trials, but further animal trials are needed to understand the mechanism(s) of action. Our major funders include the National Institutes of Health, the Department of Defense, the Michael J. Fox Foundation, the Cure Parkinson’s Trust UK, and H. Lundbeck A/S. VAN ANDEL RESEARCH INSTITUTE SCIENTIFIC REPORT | 39

Publications by Year