Neuroinflammation can be induced by infection, traumatic brain injury, aggregated proteins (amyloid), cellular stress, and other CNS abnormalities. It plays plays a key role in neurodegeneration and functional impairment in brain diseases.
The microglial NLRP3 inflammasome is consists of several proteins - including NLRP3 and ASC - that together results in activation of caspase-1. This ultimately leads to secretion of interleukin-1β, initiating a pro-inflammatory response around the microglia. Inflammasome activation is observed in the presence of cellular stress, amyloid plaques, and tau pathology.
At Sylics, we have developed a rapid model for testing NLRP3 inflammasome inhibitors. This consists of treating mice peripherally with the neurotoxin MPTP, which leads to robust inflammasome activation in the vicinity of dopaminergic neurons of the substantia nigra.
Reactive microglia and microgliosis
Microglia are the principal immune cells in the brain and play key role in both physiological and pathological conditions. They react to any sign of abnormality or damage in the CNS, often leading to local increases in the their numbers (microgliosis). They are thought to play a critical role in neurodegeneration in conditions like Alzheimer's and Parkinson's disease.
Sylics can assess microglia function in a wide variety of mouse models of CNS disorders. We have observed microgliosis in mouse models of Alzheimer's disease, Parkinson's disease, and vanishing white matter. We also have extensive experience with double labeling with more specific markers of reactive microglia (e.g. CD68, ASC).
Reactive astrocytes and astrogliosis
Astrocytes play an important role in synaptic homeostasis, the flow of CSF, and metabolism in the brain. In addition, astrocytes are increasingly recognized to have important immune functions and cross-signaling with other immune cells (e.g. microglia). An increased density of reactive astrocyte marker GFAP can be observed in the presence of neuroapathology.
Sylics has observed increased astrocyte reactivity in a mouse model of amyloid plaque pathology. We and our collaborators have also demonstrated astrocytic abnormalities in a mouse model of vanishing white matter. GFAP staining can therefore be a valuable readout in a wide range of disease models associated with neuroinflammation- and degeration.
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