Study confirms 20 year-old hypothesis on the brain using lactate for energy.
In comparison to other organs, the human brain has the highest energy requirements. The supply of energy for nerve cells and the particular role of lactic acid (lactate) has been a matter of intense research for many years. A hypothesis from the 1990’s postulates, that a well-orchestrated collaboration between two cell types, astrocytes and neurons, is the basis of brain energy metabolism.
It is known that astrocytes produce lactate, which flows to neurons to cover their high energy needs. However, due to a lack of experimental techniques, it remained unclear whether an exchange of lactate existed between astrocytes and neurons. Now, a study from researchers at the University of Zurich has confirmed the 20-year old hypothesis by showing that nerve cells cover their high energy demand with glucose and lactate. The team state they have shown for the first time in the intact mouse brain evidence for an exchange of lactate between different brain cells. The opensource study is published in the journal Cell Metabolism.
The current shows that by increasing the extracellular pyruvate concentration, outward transport of lactate is stimulated. Results show that lactate levels only changed in astrocytes and not in neurons; based on this finding and on results from several control experiments, a clear lactate gradient between astrocytes and neurons was confirmed. Data findings show that lactate transport by monocarboxylate transporters (MCTs) is a passive transport, such a concentration difference is a necessary condition for a lactate flux to be present.
The lab explain that entry and exit of lactate into and out of cells of the body is concentration dependent and is mediated by the specific lactate transporter, MCT. They go on to add that a typical property of certain transporter proteins is called trans-acceleration, with MCTs being imagined as revolving doors which turn faster when more people enter or exit; they made use of this property and accelerated the ‘revolving doors’.
The group validated this by using a novel fluorescent protein that binds lactate, thereby changing the amount of light released by the fluorescent molecule, this way the lactate concentration could be measured in single cells. To achieve this the researchers expressed the lactate sensor in astrocytes or neurons in the brain of anesthetized mice and measured the fluorescence changes with a special two-photon microscope.
The team surmise that more than 20 years after the formulation of the hypothesis that neurons metabolize lactate, the researchers have made an important step closer to final proof of this hypothesis. For the future, the researchers state that numerous brain diseases have been associated with metabolic deficits and their findings underlines the importance of an accurate understanding of the processes contributing to brain energy metabolism at the cellular level.
Source: University of Zurich