Firing Nerve Fibers in the Brain Are Supplied with Energy on Demand

To rapidly transmit electrical signals in the brain, the long nerve fibers are insulated by specialized cells called oligodendrocytes. These cells also respond to the electrical signals of active nerve fibers and provide them with energy on demand, as UZH researchers have discovered. If this process, regulated by potassium, is disabled in mice, the nerve fibers are severely damaged as the animals age – resembling the defects of neurodegenerative diseases.

Brain function depends on the rapid transmission of electrical signals along the axons. These long extensions of nerve cells connect billions of brain cells with each other. To ensure fast and efficient signal transmission, the axons are encased and insulated by special cells: the oligodendrocytes.

Oligodendrocytes sense and respond to the electrical signals

Now a team of neuroscientists led by Aiman Saab at the Institute of Pharmacology and Toxicology at the University of Zurich (UZH) has discovered a new central function of these insulating cells in the mouse brain: "The oligodendrocytes not only perceive the signals of active nerve fibers, but also react directly to them by accelerating the consumption of the primary energy source glucose," says Saab. They therefore supply energy-rich molecules to the fast-firing axons to cover their dynamic energy requirements.

Potassium is key signal that activates oligodendrocytes

In order to understand how active axons communicate with the oligodendrocytes surrounding them, the researchers examined the optic nerve of the mouse. In order to observe the "firing" of the nerve fibers after stimulation and how the oligodendrocytes react to it, they used tiny biosensors: artificially produced proteins that serve as microscopic detectors for molecular changes. "This allowed us to show that potassium is the key signal that activates the oligodendrocytes. It is released by the axons during firing," says Zoe Looser, the first author of the study.

Missing potassium channels lead to nerve fiber damage

The researchers also identified a specific potassium channel called "Kir4.1" as a key player in the communication between nerve fibers and oligodendrocytes. To investigate its role, the team used genetically modified mice that lacked these channels in the oligodendrocytes. In these mice, axons showed reduced lactate levels and responded less to the increase in lactate during activation. Lactate is an important by-product of glucose metabolism and indicates how fast this process is running. "The missing potassium channels led to reduced glucose metabolism in the nerve fibers and ultimately, when the mice aged, to severe axonal damage," adds Looser.

How age and diseases affect nerve fiber health

Oligodendrocytes thus play a key role in regulating the metabolic processes in the axons, which are essential for healthy nerve connections in the brain. In addition, glucose not only supplies the axons with energy, but also supports protective mechanisms against cell damage caused by oxidative stress. "If the glucose metabolism in the nerve fibers is disturbed due to damage in the oligodendrocytes, this can cause long-term nerve cell damage. This is comparable to nerve cell damage that occurs in old age and in neurodegenerative diseases such as multiple sclerosis and Alzheimer's," says Aiman Saab. The researchers now want to investigate this connection in more detail.

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