Microglia: the sentinels of the brain. Dr. Domenico Pratico' MD, FCPP
- praticolabalzheime
- 2 days ago
- 4 min read
Our brain is considered a “protected” organ in the body since it is surrounded by an anatomical structure, made of different cell types that controls what can go inside and what can exit. The structure is called “the blood brain barrier” and as the name suggests, it is a “barrier” that acts like a gatekeeper to the brain.
Normally, it keeps harmful things out and hold “good” things in. It also controls how various chemical molecules (including compounds we need or even make ourselves) enter and exit the brain.
However, when it comes to directly monitoring the “integrity” and “health” of our brain from the inside there are highly specialized cells that inhabit this organ and act as sentinels that constantly check the surrounding, which we call “microglia”.
Microglia are the main immune cells in our brain, where they play a fundamental role in regulating the defense and protection by orchestrating the inflammatory reactions (neuroinflammation) in response to internal and external harmful agents.
In short, microglia cells are the guardians of our brain!
In their resting state, they extend branches like antennae to continuously survey the brain environment, but they can rapidly become activated in response to damage or infection they became more rounded. In general, timely and balanced microglial activation is necessary for brain healthy functioning, homeostasis but also for repair after an injury, such as a stroke.
However, at times microglia can also play a dual, almost ambivalent role: they can block neuroinflammation or, conversely, exacerbate it. They can therefore protect or damage our brain in the same individual!
This dual behavior is further complicated by a network of internal and external molecular and chemical mediators (i.e., chemokines and cytokines) that influence their function, directing it toward the protection or the damage and toxicity.
In fact, while beneficial in most cases, chronic or excessive activation of microglia can lead to chronic inflammation and subsequent damage of the brain tissue. Recent studies have highlighted this dual role of microglia also in neurodegenerative diseases like Alzheimer's disease. In the early stages of the disease, they are typically protective, however with time they can change behavior completely and start inducing damage instead of repair or protection.
Here is a brief summary of the good deeds that they can perform in the brain.
Phagocytosis, or “clean up". They help clear amyloid-beta peptides and tau proteins, which are hallmarks of Alzheimer’s disease. When microglia detect a problem, they transition from a ramified shape to a more amoeboid (round, mobile) form. This allows them to migrate to the site of injury or infection and perform a clean-up process called phagocytosis. This process is critical for removing debris, clearing dead cells, protein aggregates, and other metabolic waste; eliminating pathogens like microbes that may have entered the brain.
Regulating neuronal function. Microglia are involved in communication with nerve cells and other brain cells, regulating various neuronal activities: formation of new nerve cells and communication between nerve cells.
Anti-inflammatory response. They release anti-inflammatory factors and neurotrophic factors that support neuronal health. Once the threat is neutralized, they switch to an anti-inflammatory state, releasing factors (e.g., interleukin-10) that help resolve inflammation and promote tissue repair.
However, as the disease progresses, microglia become chronically activated and become harmful.
Neuroinflammation. This chronic activation leads to a sustained release of pro-inflammatory cytokines (like TNF-α and IL-6), which are damaging and toxic to nerve cells.
Neuronal damage. The resulting neuroinflammation contributes to synaptic dysfunction, neuronal death, and the progression of neurodegeneration.
At time, the same sequence of events described above can easily create a vicious cycle where the accumulation of amyloid beta triggers inflammation, which in turn impairs the microglia's ability to clear the amyloid beta itself, further fueling the inflammation and disease progression. Some evidence would suggest that this chronic inflammatory state is a key driver of Alzheimer's disease pathogenesis and the associated cognitive decline.
Can we target microglia for therapeutic benefit?
Based on the current knowledge on these cells and their behavior in health and disease, research effort is being made to target them pharmacologically. In particular, scientists are testing the viability and efficacy that various classes of drug known to have powerful anti-inflammatory action may have against these cells in preventing or slowing down the progression of Alzheimer’s disease. Additional effort is being made in an attempt to promote the protective phenotype of microglia. Thus, new experimental research is exploring ways to shift microglia away from the damaging behavior and more toward their protective, anti-inflammatory state to slow or reverse the disease progression.
In conclusion, like for many other aspects of cell biology, in the case of microglia the balance between activation and resting state is key for health and wellness both at the cellular and organ level.
If you are interested in reading more of my blogs:
Check out my recent blog: The 4 Cardinal Points of Behavior Domenico Pratico', MD, FCPP
Domenico Praticò, MD, holds the Scott Richards North Star Charitable Foundation Chair for Alzheimer’s Research and serves as a Professor at the Alzheimer’s Center at Temple, as well as a Professor of Neural Sciences at Lewis Katz School of Medicine at Temple University.
For more information on the research conducted by Dr. Domenico Pratico, please visit this link.
Connect with Dr. Domenico Pratico through LinkedIn, Facebook, Twitter, Medium.
Stay updated with the work happening at Dr. Domenico Pratico's lab by visiting the Pratico Lab website.
Comments