Background
Microglia are the resident immune cells of the central nervous system (CNS) and are key players in the neuroinflammatory response. In neurodegenerative diseases, microglia can become inflamed. In the case of Alzheimer's disease, microglia become inflamed in response to β-amyloid plaques and neurofibrillary tangles.
This inflammatory response can be beneficial in combating pathogens or in the clearing of cellular debris, but chronic or sustained neuroinflammation may contribute to neuronal damage and the progression of neurodegenerative disease over time.
How We Study Microglia & Neuroinflammation
Microglia Imaging and Identification
Translucence Biosystems utilizes our modified iDISCO+ protocol for whole-brain immunostaining of microglia using an Iba1 antibody to visualize microglia activation throughout the entire brain. Brighter and more condensed microglia indicate activation, as observed in mice treated with the inflammation-inducing agent, lipopolysaccharide (LPS).
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AI-Powered Microglia Segmentation and Quantification
The Translucence Teravoxel ToolKit (3TK), a part of our VoxelsTM software, uses AI-powered workflows for automated brain-wide identification of microglia. The 3TK software detects Iba1 immunoreactivity in intact 3D brains and generates cell labels, enabling quantification of microglial counts, morphological analysis, and fluorescence intensity measurements. Each brain and its segmented cells are then computationally warped to the Allen Reference Brain to provide Iba1 expression metrics across hundreds of brain regions.
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Coronavirus
Translucence Biosystems, in collaboration with the Lane lab at UC Irvine, has studied the neuroinflammation in response to infection with the murine coronavirus, MHV (murine hepatitis virus). Optical slices through infected brains reveal brain-wide neuroinflammation in response to viral treatment, with clear regional patterns of microglial activation, compared to control brains.
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Alzheimer's Disease
In Alzheimer's 5xFAD mouse model brains, which highly express β-amyloid plaques, Iba1(+) microglia colocalize with β-amyloid plaques and become activated. This activation is characterized by the retracting of processes and distinct morphology not seen in wild-type (WT) mouse brains.
To quantify plaque associated microglia (PAM), we trained our Al-powered workflows to selectively detect them while excluding the majority of the homeostatic Iba1(+) microglia. Visit our AI-powered Quantification page to learn more about AI-powered workflows.
The PAM levels in Cerebellum, Visual, and Somatomotor areas are consistent with the β-amyloid levels detected in the same mice. Across hundreds of brain areas, the data from our β-amyloid and PAM whole-brain quantification workflows are strongly correlated.
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Summary
By leveraging tissue clearing, light sheet imaging, and AI-powered quantification, Translucence Biosystems provides insights into the role of microglia and neuroinflammation in various pathological conditions.
