Historically viewed as the immune system’s foot soldiers, microglia are now recognized by scientists as pivotal players in brain health and disease. Research suggests these small cells may influence a range of conditions, from addiction and chronic pain to Alzheimer’s disease, depression, anxiety, long COVID, and myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome.
So, what are microglia? They are the smallest members of the glial cell family, accounting for about 10% of all brain cells. While neurons serve as the brain’s messengers, transmitting information via electrical impulses, microglia take on a supportive role. These cells have a central oval-shaped body with slender, tendril-like arms that continually survey their environment.
Paolo d’Errico, a neuroscientist at the University of Freiburg, explains, “They have a lot of branches that they are continually moving around to survey their environment.” When functioning optimally, microglia are crucial for healthy brain function, pruning unnecessary synaptic connections during brain development, repairing myelin (the protective layer around neurons), and guarding against infection by destroying harmful bacteria and viruses.
Microglia also play a vital role in clearing debris and eliminating toxic proteins like amyloid plaques, which are implicated in Alzheimer’s disease. However, their protective role can become problematic under certain conditions. Linda Watkins, a neuroscientist at the University of Colorado Boulder, highlights the dual nature of microglia, stating, “There are good and bad sides to microglia.”
When microglia sense abnormalities, such as infections or amyloid plaques, they enter a hyper-reactive state, enlarging and becoming more active. “They pull in their appendages and start moving around, munching up damage like little Pac-Mans,” says Watkins. Activated microglia release inflammatory cytokines, signaling other immune cells to join the fight against perceived threats. Typically, they return to their resting state after a threat subsides; however, sometimes they remain activated, contributing to various diseases.
This activation may be particularly relevant in the context of addiction. Traditionally viewed as a disorder of the dopamine system, researchers now believe microglia may also be involved. According to Watkins and her colleagues, when individuals consume drugs, microglia perceive these substances as foreign invaders. “What we found was that various opiates activate microglial cells through what’s called the ‘toll-like receptor’ (TLR),” she explains.
The activation of TLRs leads to increased cytokine release, heightening neuronal excitability and strengthening the connections formed during drug use. This process may engrain drug-seeking behaviors, changing the brain’s architecture and potentially leading to lifelong addiction.
Supporting evidence includes heightened inflammation in drug abusers’ brains and studies showing that reducing inflammation can decrease drug-seeking behavior in animals. By blocking TLR receptors, researchers have successfully halted drug-seeking behavior in mice, suggesting a novel approach to understanding and potentially treating addiction.
As research into microglia continues to evolve, their significant role in brain function and health is becoming increasingly clear, presenting new opportunities for addressing a range of neurological disorders.
