Center for Brain and Spinal Cord Repair, Institute for Behavioral Medicine Research

GodboutJonathanAssistant Director for Basic Science, Institute for Behavioral Medicine Research
Associate Professor, Center for Brain and Spinal Cord Repair
Associate Professor, Department of Neuroscience

College of Medicine
Department of Neuroscience

Google scholar articles
PubMed articles

259 Institute for Behavioral Medicine Research Building
460 Medical Center Drive
Columbus, OH 43210
Phone: 614-293-3456
Email: Jonathan.Godbout@osumc.edu

My Research Lab: Godbout Lab for Neuroimmunology, Neurotrauma, and Behavior

Current Research:
1. Aging Neuroimmunology
Microglia and astrocytes are key cells that recognize, interpret, propagate and regulate immune responses. In the elderly, peripheral infections can trigger delirium and behavioral disturbances. Moreover, ongoing inflammatory processes in the elderly are associated with depressive-like complications. These complications are not a normal part of aging and negatively affect quality of life and life-span. Impaired regulation of microglia could cause this altered communication between the immune system and the aged brain.
We have identified astrocytes as the pivotal cell in the failure to resolve microglial activation in the aged brain following immune challenge. Activated astrocytes in the aged brain have reduced sensitivity to IL-10, an anti-inflammatory cytokine, and decreased IL-10 receptor-1 expression.  This IL-10 insensitivity of aged astrocytes results in failure to produce TGFα and attenuate microglial activation. We are testing the hypothesis that prolonged neuroinflammation in the aged brain following a peripheral inflammatory challenge is caused by impaired astrocyte-dependent regulation of microglia. Understanding how impaired IL-10 re-programming of astrocytes contributes to neuroinflammation and depressive-like behavior will lead to new interventions that target astrocytes in order to reduce neuropsychiatric complications associated with inflammatory challenge in the aged.
2. Brain Injury and Intervention Project
Traumatic brain injury (TBI) can lead to secondary neuropsychiatric complications that develop and persist years after injury. Mounting evidence indicates that neuroinflammatory processes continue to advance after the initial head injury and can worsen with time and are likely mediated by microglia and astrocytes. Therefore, it is critical to identify interventions that can be provided immediately after TBI that reduce glia-mediated inflammation, facilitate functional recovery, and reduce the development of TBI-induced long-term complications in behavior, cognition, and pathology.
Immediate intervention with methylene blue (MB), an antioxidant and anti-inflammatory agent, reduces neuroinflammation in mice after moderate and diffuse TBI, improves functional recovery, and limits the development of a primed and reactive microglia 1 month after injury. We are investigating the degree to which MB intervention shifts the activation profile of microglia and astrocytes and protects against secondary complications following TBI including cognitive decline, glia-mediated inflammation, and glial reactivity to immune challenge.
3. STRESS NEUROIMMUNOLOGY
Brain region dependent trafficking of myeloid cells following repeated social defeat

Project Summary/Abstract: Psychosocial stressors are associated with an increased prevalence of mental health complications including anxiety and depression. Although chronic stressors negatively affect health and influence quality of life, the mechanisms that underlie these neurobehavioral deficits are not well understood. Repeated social defeat (RSD)-induced anxiety-like behavior is associated with the egress and trafficking of bone marrow (BM)-derived, glucocorticoid (GC)-insensitive myeloid cells to the brain. Moreover, RSD promotes the infiltration of CD11b+/Ly6Chigh/CCR2+ myeloid cells to specific brain regions associated with fear and threat appraisal.  IL-1 receptor type-1 (IL-1R1) and -adrenergic receptor (-ADR)-dependent pathways are critical in the development of behavioral and immunological alterations promoted by RSD. We are testing our hypothesis that repeated social defeat stimulates trafficking of primed GC-insensitive, CD11b+/LyC6high/CCR2+ myeloid cells from the bone marrow to fear and threat appraisal regions in the brain to promote prolonged anxiety-like behavior.

To address this hypothesis, we are using a mouse model of repeated social defeat to understand how stress-associated promotion of myeloid cell trafficking contributes to neuroinflammation and the promotion of long-lasting anxiety-like behavior. This understanding could lead to novel interventions to target myeloid cell trafficking and attenuate prolonged neurobehavioral complications associated with chronic stress.

Research Techniques: Cell Flow Cytometry; FAC-Sorting; Immunohistochemistry; Neurochemistry; RNA analysesl; ELISA; Bone marrow chimeras; Microglia; Astrocyte, and macrophage specific isolations; Fluid Percussion Injury; Glia Cultures; Behavioral and Cognitive analyses

Active Funding:
1.  Co-investigator, R01, NIH/National Institute of Mental Health
1/01/12 -12/30/17
“Social Threat Primes Myeloid Progenitor Cells and Microglia: Role in Anxiety”

2. Co-investigator, R01
NIH/National Institute of Nursing Research.
3/01/12-2/28/17        
“Muscle Function and Depression-Like Behavior in a Mouse Model of Cancer Fatigue”

3. Co-investigator, R01
4/01/13 – 3/31/18
Source: NIH/National Institute of Mental Health
Brain region dependent trafficking of myeloid cells following repeated social defeat
Role: Co-Investigator (4 Calendar months per year)

4. Co-investigator, R21 9/15/14 -9/14/16
NIH/NINDS         
“Peripheral Trafficking in Locomotor Networks After Thoracic SCI”

5. Co-PI, Nationwide/COM Cross Campus Collaborative Pilot Program
OSUMC/Nationwide Children’s Hospital     04/01/15-3/30/16
 “Effects of Perinatal Inflammation on Microglia Responses in Adulthood”

6. Co-investigator, R21  05/18/2015 – 02/28/2017   .NIH/NIMH   
“Social Modulation of Microglia”

7. Co-investigator, R01 12/1/15-12/1/20 
NIH/NIMH      
“Anxiety, IL-1R1, and Neuroinflammation”     

8. Co-investigator, R01 NIH      
“Affective Consequences of Chemotherapy”

Education:
BS, Cell and Structural Biology, University of Illinois, 1996
PhD, Biochemistry/Signal Transduction, University of Illinois, 2001
Fellowship: Postdoctoral Research, Rodney W. Johnson, PhD, University of Illinois, 2001-2005, Ruth L. Kirschstein NRSA Postdoctoral Fellowship, 2003-2005

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