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Updated: May 2, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglial priming in neurodegenerative disease
1Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Tremona Road, Southampton SO16 6YD, UK.
Abstract:
Under physiological conditions, the number and function of microglia--the resident macrophages of the CNS--is tightly controlled by the local microenvironment. In response to neurodegeneration and the accumulation of abnormally folded proteins, however, microglia multiply and adopt an activated state--a process referred to as priming. Studies using preclinical animal models have shown that priming of microglia is driven by changes in their microenvironment and the release of molecules that drive their proliferation. Priming makes the microglia susceptible to a secondary inflammatory stimulus, which can then trigger an exaggerated inflammatory response. The secondary stimulus can arise within the CNS, but in elderly individuals, the secondary stimulus most commonly arises from a systemic disease with an inflammatory component. The concept of microglial priming, and the subsequent exaggerated response of these cells to secondary systemic inflammation, opens the way to treat neurodegenerative diseases by targeting systemic disease or interrupting the signalling pathways that mediate the CNS response to systemic inflammation. Both lifestyle changes and pharmacological therapies could, therefore, provide efficient means to slow down or halt neurodegeneration.
Insights
Microglia, the brain's immune cells, become primed during neurodegeneration. This priming makes them overreact to secondary inflammation, offering new therapeutic targets for neurodegenerative diseases.
Area of Science:
- Neuroimmunology
- Neuroinflammation
- Cellular Biology
Background:
- Microglia, the central nervous system (CNS) resident macrophages, normally maintain a controlled state.
- Neurodegeneration and protein misfolding trigger microglial proliferation and activation, a process termed priming.
- Primed microglia exhibit heightened susceptibility to secondary inflammatory stimuli.
Purpose of the Study:
- To explore the concept of microglial priming in the context of neurodegeneration.
- To investigate the mechanisms driving microglial priming and their exaggerated response to inflammation.
- To identify potential therapeutic strategies for neurodegenerative diseases by targeting microglial priming and systemic inflammation.
Main Methods:
- Review of preclinical animal models investigating microglial responses to neurodegenerative conditions.
- Analysis of molecular mechanisms underlying microglial priming and activation.
- Examination of the role of the microenvironment and systemic factors in modulating microglial inflammatory responses.
Main Results:
- Microglial priming is driven by microenvironmental changes and molecular signals associated with neurodegeneration.
- Primed microglia mount an exaggerated inflammatory response upon secondary stimulation, particularly from systemic inflammation in elderly individuals.
- This priming phenomenon provides a mechanistic link between systemic inflammation and neuroinflammation.
Conclusions:
- Microglial priming is a critical factor in the neuroinflammatory response to neurodegeneration.
- Targeting systemic inflammation or the CNS signaling pathways involved in microglial priming offers promising therapeutic avenues.
- Lifestyle modifications and pharmacological interventions hold potential for slowing or halting neurodegeneration by modulating microglial activity.
