Several studies presented at SfN Neuroscience (19–23 October 2019, Chicago, IL, USA) have shed light on how changes in microglia impact both neuroinflammation and disease pathology in mice.
“This represents research that helps us understand the underpinnings and mechanisms of neuroinflammation,” commented press conference moderator, Donna Wilcock (University of Kentucky, KY, USA). “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.”
Could an inflamed cerebellum be linked to behavioral disorders in mice?
In a mouse model, researchers have discovered that immune activity in the cerebellum induces neuronal hyperexcitability and disrupts psychomotor behaviors.
It is well established that cerebellar dysfunction is involved in various psychiatric disorders, including autism spectrum and depressive disorders, however, our understanding of the physiological aspect is less advanced.
In this study, the team of researchers utilized activated microglia that had been exposed to bacteria, which induced intrinsic excitability in Purkinje neurons. The team observed that this excitability was suppressed by microglia activity inhibitor and microglia depletion and that the release of TNFα triggered this plasticity.
Furthermore, the team observed region-specific inflammation in the cerebellum that indicated depression- and autistic-like behaviors in vivo. This modulation was reverted by microglia depletion as well as TGFα inhibition.
Overall, the team suggest that the results illustrate that an inflamed cerebellum may be related to behavioral disorders, including depression and autism spectrum disorders. Prefrontal cortex activity also increased, indicating the cerebellum is connected to higher-order brain function.
Abstract: Ohtsuki G, Yamamoto M, Kim M, Imai H, Itakura Y. Microglia-triggered plasticity of intrinsic excitability modulates psychomotor behaviors in acute cerebellar inflammation. Presented at: SfN Neuroscience, Chicago, IL, USA, 19–23 October 2019.
Novel property of aspirin discovered in upregulating IL-1Ra in rodent glial cells
A team of researchers have discovered a novel property of aspirin in upregulating IL-1Ra in glial cells of mice via PPARα.
IL-1Ra is known to be a protective molecule that prevents neuroinflammation, a hallmark of different neurodegenerative disorders. In this study, rodents that were fed aspirin demonstrated improved learning and memory.
The findings suggest that aspirin could be utilized as a treatment option for neuroinflammatory and neurodegenerative disorders. However, as PPARα controls fat metabolism, those individuals who are deficient in PPARα may experience a varying level of treatment effectiveness.
Abstract: Pahan K, Chakrabarti S, Roy A, Prorok T, Patel DR, Dasarathy S. Aspirin upregulates IL-1Ra in glial cells via PPAR-α. Presented at: SfN Neuroscience, Chicago, IL, USA, 19–23 October 2019.
Sensory lesioning induces microglial synapse elimination in mice
Researchers have identified a mechanism by which microglia engulf and eliminate synapses in the somatosensory cortex, following peripheral sensory deprivation.
The team identified that removing whiskers from rodents reduced synaptic connections, thereby decreasing communication within the brain. The synapses were removed from the brain by microglia.
Furthermore, they demonstrated that the microglial chemokine receptor, CX3CR1, is necessary for whisker deprivation-induced microglial engulfment. Following the removal of whiskers, CX3CL1 molecules and the molecule regulating it (ADAM10) were observed in higher concentrations in the brain. Blocking both molecules protected the synapses from being destroyed.
Together, the results provide new insights into the functionality of microglia and how neural circuits respond to changes in the sensory environment. The findings also reveal how CX3CR1–CX3CL1 regulates microglial function at synapses in an activity-dependent manner.
Abstract: Gunner G, Cheadle L, Johnson KM et al. Sensory lesioning induces microglial synapse elimination via ADAM10 and fractalkine signaling. Presented at: SfN Neuroscience, Chicago, IL, USA, 19–23 October 2019.
Source: Society for Neuroscience. Changes in microglia impact neuroinflammation and disease pathology. Press release: www.sfn.org/Meetings/Neuroscience-2019
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