Microglia are essential for spreading depression
Microglia play an important role in fine-tuning neuronal activity. Recent work from our lab shows that microglia are essential for spreading depression.
IGF-1 abrogates SD and microglial responses to SD
Insulin-like growth factor-1 abrogates microglial oxidative stress and TNF-α responses to spreading depression. Grinberg YY et al. (2013) Journal of Neurochemistry
Phasic treatment with IFNγ stimulates release of exosomes from microglia that are protective
Phasic treatment with IFNγ increases microglial (arrow heads) glutathione (arrows) in hippocampal slice cultures.
Our research centers on understanding how the brain can protect itself against neurological diseases (e.g., Alzheimer’s, Parkinson’s, stroke, multiple sclerosis, epilepsy, and migraine) and cognitive decline from aging. Brain is unique among organ structures. It can alter its regional, cellular, and molecular function as well as structure in response to activity. This is classically evidenced by Hebbian synaptic plasticity. However, it also extends to include environmental enrichment (i.e., increased intellectual, social, and physical activity), which protects the brain against neurological disease. Though incompletely defined, the mechanisms by which naturally increased brain activity strengthen brain involve immune signaling, the focus of our work.
Brain and immune functions are highly interactive and symbiotic, a relationship most often recognized in association with disease. For example, depressed mood reduces immune function and enhances susceptibility to disease. Also, increased immune function after disease onset worsens brain function. However, under physiological conditions, immune activation is nutritive when it is low-level and occurs over time, which allows for adaptation. This latter process is known as physiological conditioning hormesis. In fact, immune signaling is essential for the improved learning and memory associated with enrichment.
Our projects explore how enrichment triggers low-level pro-inflammatory immune signaling associated with oxidative stress which, over time, strengthens brain. We use whole animal and in vitro models. In addition, we use cellular and molecular imaging strategies as well as genomic and proteomic techniques and computational analyses of data from these approaches to search for the “signaling syntax” by which natural neural activity makes brain more resilient to disease. Our tools include time-lapse vital cellular imaging, laser dissection microscopy, real-time RT-PCR, semi-quantitative cellular cytological and immunohistochemical imaging, proteomic tools (including bead-based ELISAs), and novel neural therapeutic delivery systems.
Our hope is that the knowledge gleaned from these projects will empower healthcare providers and patients with evidence-based strategies that effectively enhance neurological health. Furthermore, this knowledge will help to develop novel therapeutics based on how the brain works best to preserve its health.
Specific research projects:
- The mechanisms and consequences of migraine, modeled via spreading depression
- The mechanisms by which enrichment results in neuroprotection
- The mechanisms by which enrichment mitigates the impact of neonatal ischemic brain injury
- Development of enrichment-based neural therapeutics
Prevention (Sep 2015) 6-health-risks-linked-migraines
ITM (July 2015) See who won $150K
Chicago Innovation Exchange (July 2015) UChicago Innovation Fund gives over 500k to three impact startups
New Scientist (Feb 2015) Brain boosting: It’s not just grey matter that matters
UC magazine: Protein enriched (2014)
Scientific American: Naturally occurring packets show promise for protecting brain nerve fibers (2014)
exRNA Research Portal: Exosome RNA therapeutics to promote CNS myelination (2014)
Society for Neuroscience: Potential treatments for multiple sclerosis (2013)
MedPageToday: New therapy for MS on horizon? (2013)
U of C Science Life: New particle to fight MS and brain aging (2013)
From the UChicagoTech: A new approach to migraine therapy (2012)
February 1st, 2012: A Nasal Path to Migraine Relief
Tech Transfer Central: Breakthrough in chronic migraine relief (2012)
Chicago Health: The brain at war (2011)