Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have now discovered exactly how microglia detect the site of injury, thanks to a relay of molecular signals. Their work, published today in Developmental Cell, paves the way for new medical approaches to conditions where microglia’s ability to locate hazardous cells and material within the brain is compromised.
“Considering that they help keep our brain healthy, we know surprisingly little about microglia,” says Francesca Peri, who led the work. “Now, for the first time, we’ve identified the mechanism that allows microglia to detect brain injury, and how that emergency call is transmitted from neuron to neuron.”
When an emergency occurs, cries can alert bystanders, who will dial the emergency number. A call will go out over the radio, and ambulances, police or fire engines in the area will respond as needed. In the brain, Peri and colleagues found, injured neurons send out their own distress cry: they release a molecule called glutamate. Neighbouring neurons sense that glutamate and respond by taking up calcium. As glutamate spreads out from the injury site, this creates a wave of calcium swallowing. Along that wave, as neurons take up calcium they release a third molecule, called ATP. When the wave comes within reach, a microglial cell detects that ATP and takes it as a call to action, moving in that direction – essentially tracing the wave backwards until it reaches the injury.
Scientists knew already that microglia can detect ATP, but this molecule doesn’t last long outside of cells, so there were doubts about how ATP alone could be a signal that carried far enough to reach microglia located far from the site of injury. The trick, as Peri and colleagues discovered, is the long-lasting glutamate-driven calcium wave that can travel the length of the brain. Thanks to this wave, the ATP signal is not just emitted by the injured cells, but is repeatedly sent out by the neurons along the way, until it reaches microglia.
Dirk Sieger and Christian Moritz in Peri’s lab took advantage of the fact that zebrafish have transparent heads, which allow scientists to peer down a microscope straight into the fish’s brain. They used a laser to injure a few of the fish’s brain cells, and watched fluorescently-labelled microglia move in on the injury. When they genetically engineered zebrafish to make neurons’ calcium levels traceable under the microscope, too, the scientists were able to confirm that when the calcium wave reached microglia, these cells immediately started moving toward the injury.
Knowing all the steps in this process, and how they feed into each other, could help to design treatments to improve microglia’s detection ability, which go awry in conditions such as Alzheimer’s and Parkinson’s diseases.
Sonia Furtado Neves | EMBL Research News
Zap! Graphene is bad news for bacteria
23.05.2017 | Rice University
Discovery of an alga's 'dictionary of genes' could lead to advances in biofuels, medicine
23.05.2017 | University of California - Los Angeles
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...
23.05.2017 | Event News
22.05.2017 | Event News
17.05.2017 | Event News
23.05.2017 | Life Sciences
23.05.2017 | Medical Engineering
23.05.2017 | Life Sciences