The microglial sensome revealed by direct RNA sequencing

Area of Science:

• Neuroscience
• Immunology
• Aging Research

Background:

• Microglia are the brain's primary immune cells, constantly monitoring their environment.
• They possess plasticity, adopting states that influence their response to threats.
• Understanding microglial function is crucial for brain health, especially during aging.

Purpose of the Study:

• To investigate the quantitative transcriptomes of microglia in adult and aged mice.
• To identify the unique molecular signature, or 'sensome,' of microglia.
• To characterize age-related changes in microglial gene expression and function.

Main Methods:

• Direct RNA sequencing without amplification or cDNA synthesis for quantitative transcriptomics.
• Validation using fluorescence dual in situ hybridization, proteomic analysis, and quantitative PCR.
• Comparative analysis of microglia from healthy adult and aged mice.

Main Results:

• Microglia possess a distinct transcriptomic signature, termed the 'sensome,' involved in sensing endogenous ligands and microbes.
• Aging led to downregulation of sensome transcripts for endogenous ligand recognition.
• Aging upregulated sensome transcripts for microbe recognition and host defense, alongside increased expression of neuroprotective genes.

Conclusions:

• Microglial sensome composition shifts significantly with age.
• Aging microglia show a reduced capacity for recognizing endogenous signals but an enhanced response to microbial cues.
• These age-related transcriptomic changes may contribute to altered neuroimmune function and neuroprotection in aging brains.