Understanding These Immune Cells May Lead to New Ways to Treat Brain Diseases

Somewhere in your brain, immune cells (like the one below) are on patrol, crawling around your neurons on the lookout for debris that’s piling up, bacteria that have snuck in, even neurons that are malfunctioning.

image of a microglial cell

A microglia cell before activation. Image: Francesca Bartolini/Columbia University.

Before these cells, called microglia, can clear the debris or invaders, they must be activated—and in the process the long narrow cells undergo a dramatic change in shape, drawing up into a round, flat disk, like an amoeba.

Scientists know little about what happens inside the cell to achieve this transformation, partly because it’s been nearly impossible to observe sensitive microglia under a microscope without accidentally activating or deactivating them. But learning how microglia activate may lead to new ways to slow the progression of brain diseases, since microglia stuck in an activated state are believed to play a role in diseases like Alzheimer's, Parkinson's, and ALS.

One way to counteract overactive microglia may be to target their cytoskeletons, according to new research from Francesca Bartolini, PhD, associate professor of pathology & cell biology at Columbia University Vagelos College of Physicians and Surgeons, and collaborators from Sapienza University of Rome and the Italian Institute for Technology.

Bartolini’s team and collaborators devised a way to grow and image the microglia without overly perturbing them and saw that what makes microglia’s shape shifting possible is a complete reorganization of the cell’s microtubule cytoskeleton.

In unactivated microglia, these microtubules, which give the cells support and guide organelle transport, are arranged in parallel. But during activation, the microtubules suddenly arrange themselves like spokes in a bicycle wheel.

circular array of microtubules

Microtubules must arrange themselves into a radial pattern during microglia activation. Activated microglia are important in keeping the brain healthy, but microglia that are stuck in an activated state are believed to inflame the brain and cause neurodegeneration in diseases like Parkinson's and Alzheimer's. The new study suggests that targeting microtubule reorganization could prevent microglia activation and potentially slow disease. Image: Francesca Bartolini/Columbia University.

Without this massive microtubule reorganization, microglia cannot be activated.

The new study suggests that targeting the microtubule reorganization could prevent microglia activation and potentially slow some brain diseases.

The study will also help researchers determine if damage caused by chemotherapeutic drugs to the microtubules in spinal microglia contributes to peripheral neuropathy experienced by many cancer patients.


More information

The findings were published Feb. 13 in Cell Reports.

The study was supported by grants from the NIH (RF1AG050658 and R21NS120076-01); a Fulbright Award (FSP-P005556); the CrestOptics-IIT JointLab for Advanced Microscopy and the D-Tails-IIT JointLab, Regione Lazio FSE grants (19036AP000000019 and A0112E0073), Sapienza University grants (RM118163E0297F84, PH12017270934C3C, and MA32117A7B698029), Fondazione Istituto Italiano di Tecnologia, and a grant from the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University.