A recent study, published in Frontiers in Molecular Neuroscience, shows the associations between brain energy metabolism and neuronal activity. A genome-wide study sheds light on different mechanisms through which lactate regulates long-term memory formation and neuroprotection.
Lactate, a product of aerobic glycolysis, is produced by the breakdown of sugar in non-neuronal brain cells, called astrocytes. This lactate gets shuttled to neurons which are then used as an energy source.
Lactate not only supports the energy stresses of neurons but also quickly and briefly triggers multiple genes. These genes are then involved in neuronal activity modulation and regulation of brain function.
Former studies have found that lactate stimulates the genetic expression of encoding proteins. These proteins are involved in neuronal activity by signaling through N-methyl-D-aspartate (NMDA) receptors.
What did the study find?
Researcher’s latest study exposes the level to which lactate alters gene expression in cortical neurons. It also points to the ways through which lactate is involved in the modulation of brain function.
The genome-wide analysis of gene transcription discovered that lactate contact generates the expression of around 400 genes. However, some of these genes are crucial for altering brain structure and function according to internal and external influences. This process is known as neuroplasticity.
According to researchers of the study, lactate stimulates synaptic activity-dependent genes in the short-term and genes involved in regulating neuronal excitability in the long-term.
Researchers found that after an hour of lactate exposure, 113 genes were expressed differentially than controls. Among them, they found the genes known to mediate the NMDA-receptor-dependent response to neuronal activity. And those found to be involved in the mitogen-activated protein kinase (MAPK) signaling pathway which regulates neuronal survival.
NMDA receptor blocking through inhibitor MK-801 proved that 41% of the genes which are modulated by lactate after an hour was triggered in an NMDA-receptor dependent manner.
The study also exposed that NADH regulated the expression of more than 60% of the genes which were modulated by lactate after one hour. Nicotinamide adenine dinucleotide (NADH) is a by-product of the metabolic processing of lactate to pyruvate.
It is vital for the production of adenosine triphosphate (ATP) which is the energy currency of the cell. This outcome highlights the effect of the cells’ energy production process on expression and signaling of the neuronal gene.
The bottom line
In addition to gene identification stimulated in a non-NMDA-receptor dependent manner, the study also discovered upregulation in the expression of genes which are involved in neuronal excitability after six hours of lactate exposure.
According to the researchers, these genes could contribute to the development of therapeutic targets for neurodegenerative diseases, like Alzheimer’s disease, in which brain energy metabolism is altered.