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Published on: July 9, 2016
Heterogeneous expression of the triggering receptor expressed on myeloid cells-2 on adult murine microglia
Christoph D Schmid1, Lauren N Sautkulis, Patria E Danielson
1Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA Digital Gene Technologies Inc., La Jolla, California 92037, USA.
Abstract:
Microglial activation is an early and common feature of almost all neuropathologies, including multiple sclerosis, Alzheimer's disease and mechanical injury. To better understand the relative contributions microglia make toward neurodegeneration and neuroprotection, we used TOGA(R) to identify molecules expressed by microglia and regulated by inflammatory signals. Triggering receptor expressed on myeloid cells-2 (TREM-2) was among the mRNAs identified as being expressed by unactivated microglia, but down-regulated by lipopolysaccharide/interferon gamma. In the healthy CNS, not all microglia expressed TREM-2. Microglial expression of TREM-2 varied not only between brain regions but also within each brain region. Brain regions with an incomplete blood-brain barrier had the lowest percentages of TREM-2- expressing microglia, whereas the lateral entorhinal and cingulate cortex had the highest percentages. A novel form of TREM-2b that lacked a transmembrane domain was detected, perhaps indicating a soluble form of the protein. Taken together, these data suggest that (1) subsets of microglia are specialized to respond to defined extracellular signals; and (2) regional variations in TREM-2 expression may contribute to the varying sensitivities of different brain regions to similar pathological signals.
Insights
Microglia, immune cells in the brain, express Triggering Receptor Expressed on Myeloid Cells-2 (TREM-2). TREM-2 expression varies by brain region and may influence neuropathology.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglial activation is a hallmark of neuropathologies like Alzheimer's disease and multiple sclerosis.
- Understanding microglial roles in neurodegeneration and neuroprotection is crucial for developing treatments.
- Inflammatory signals significantly impact microglial function and gene expression within the central nervous system (CNS).
Purpose of the Study:
- To identify microglial-expressed molecules regulated by inflammatory signals using TOGA(R).
- To investigate the expression patterns of Triggering Receptor Expressed on Myeloid Cells-2 (TREM-2) in healthy and activated microglia.
- To explore the regional variations in TREM-2 expression within the brain and its potential implications for neuropathology.
Main Methods:
- Utilized TOGA(R) technology to profile microglial gene expression.
- Analyzed messenger RNA (mRNA) levels of TREM-2 in response to inflammatory stimuli (lipopolysaccharide/interferon gamma).
- Quantified TREM-2 expressing microglia across different brain regions in healthy CNS tissue.
Main Results:
- TREM-2 mRNA was expressed by unactivated microglia but downregulated by inflammatory signals.
- Microglial TREM-2 expression was not uniform, varying between and within brain regions.
- Regions with compromised blood-brain barriers showed lower TREM-2 expression, while the lateral entorhinal and cingulate cortex had higher percentages; a novel soluble TREM-2b form was detected.
Conclusions:
- Specific microglial subsets are specialized to respond to distinct extracellular signals.
- Regional differences in TREM-2 expression may underlie the varying susceptibility of brain areas to neuropathological insults.
- TREM-2's complex expression pattern suggests a nuanced role in microglial function and CNS disease.
