CHICAGO -- Advances in research about the brain's immune system have helped uncover the underlying foundations of neuroinflammation. These findings were presented at Neuroscience 2019, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news about brain science and health.
Neuroinflammation is a hallmark of degenerative brain diseases like Alzheimer's Disease (AD), and understanding the causes and mechanisms are critical for treating them. Microglia, immune cells in the brain, are an important part of the body's immune system and its inflammatory response. Scientists are beginning to understand how microglia respond to damage and disease, and how this response can become disordered and/or harmful. Changes in microglial cells are noted in a wide variety of neurodegenerative diseases ranging from Autism Spectrum Disorder (ASD) to AD and other forms of dementia.
Today's new findings show that:
- Microglia activated by inflammation in the cerebellum of mice trigger hyperexcitability in the brain, causing decreases in sociability, motivation, and healthy behavior (Gen Ohtsuki, Kyoto University Graduate School of Science).
- Baby aspirin given to AD mice increases the response of a protective molecule that prevents neuroinflammation, leading to improved memory and learning. These finding provide insight into the mechanism by which the medication affects the brain (Kalipada Pahan, Rush University).
- Microglia in mice with decreased sensory experience eliminate sensory experience-related synapses in the brain, unless a regulating molecule is blocked. This study provides a better understanding of the function of microglia in the brain and their role in neurodegenerative diseases (Dori Schafer, University of Massachusetts Medical School).
"This represents research that helps us understand the underpinnings and mechanisms of neuroinflammation," said press conference moderator Donna Wilcock, PhD, a professor at the University of Kentucky who studies vascular cognitive impairment and dementia. "We are only beginning to understand the complex interplay between the immune system and the brain, and we don't yet know how to manipulate it effectively. This research will further our understanding of these challenges and find a way forward to treat patients with inflammation due to disease or injury."
This research was supported by national funding agencies including the National Institutes of Health and private funding organizations. Find out more about Alzheimer's Disease and other cognitive disorders on BrainFacts.org.
Related Neuroscience 2019 Presentation
Symposium: CNS Scarring, Inflammation, and Repair
Wednesday, Oct. 23, 1:30 - 4:00 p.m., Room S100A
Glia Press Conference Summary
- This research shows how microglia and other immune regulating mechanisms can either help or harm the brain. Although the complex interactions between these cells and the rest of the brain are not fully known, this research begins to isolate and assess these relationships and identify methods to control and manipulate them in cases of disease or other causes of inflammation.
Microglia-Triggered Plasticity of Intrinsic Excitability Modulates Psychomotor Behaviors in Acute Cerebellar Inflammation Gen Ohtsuki, email@example.com, Abstract 554.09
- In a rodent model, inducing excessive immune activity increased excitability in the cerebellum while reducing sociability and other normal behaviors. By suppressing microglia and cytokine, behavior abnormalities were recovered.
- The results indicate that an inflamed cerebellum may be related to behavioral disorders, including depression and autism spectrum disorders. Furthermore, prefrontal cortex activity also increased, indicating the cerebellum is connected to higher-order brain function.
Aspirin Upregulates IL-1Ra in Glial Cells via PPAR-alpha
Kalipada Pahan, Kalipada_Pahan@rush.edu, Abstract 539.07
- In a mouse model, researchers showed that small doses of aspirin may upregulate interleukin-1 receptor antagonist (IL-1Ra), a protective molecule that prevents neuroinflammation. Rodents that were fed aspirin showed improved memory and learning.
- Interestingly, aspirin requires peroxisome proliferator-activated receptor alpha (PPARα), which controls fat metabolism, to function effectively. Without this, aspirin may not have its protective abilities. Those who are deficient in PPARα can include overweight people, and these findings can help us understand when and why treatment might not be effective.
Sensory Lesioning Induces Microglial Synapse Elimination via ADAM10 and Fractalkine Signaling
Dori Schafer, DorothyDori.Schafer@umassmed.edu, Abstract 469.19
- In a rodent model, researchers manipulated sensory experience by removing whiskers, which resulted in reduced synaptic connections and thus reduced communication in the brain. Microglia subsequently removed those synapses from the brain.
- Researchers are also beginning to understand the mechanisms underlying this microglial activity. A microglial chemokine receptor, CX3CR1, seems to be essential for engulfment to occur; after whiskers were removed, fractalkine (CX3CL1) molecules and the molecule regulating it (ADAM10, an AD risk gene) were found in higher concentrations in the brain. Blocking both protected the synapses from being destroyed.
- This shows how neural circuits respond to changes in sensory environment and sheds light on the functionality of microglia.
About the Society for Neuroscience
The Society for Neuroscience is the world's largest organization of scientists and physicians devoted to understanding the brain and nervous system. The nonprofit organization, founded in 1969, now has nearly 37,000 members in more than 90 countries and over 130 chapters worldwide.