The study, published in Nature Communications, details how metabolic alterations in astrocytes in mice affect synaptic plasticity and cause memory problems. These deficits, however, can be reversed through dietary serine supplementation.
Traditionally, the focus in learning and memory has been on neurons. However, this research highlights the importance of support cells, such as astrocytes, which significantly contribute to brain function. The investigation was conducted in the hippocampus, a brain region vital for memory formation.
Researchers removed a key protein, PI3K, from astrocytes in mice. This resulted in difficulties in spatial memory tests and a reduction in synaptic plasticity, meaning the ability of neurons to modify the strength of their connections, a crucial mechanism for neuronal adaptation during learning.
Serine, an amino acid with two forms (L-serine and D-serine), plays a central role. Neurons require D-serine to activate NMDA receptors, necessary for neuronal communication. Astrocytes are the source of L-serine, which neurons use to produce D-serine. The reduction of L-serine due to the absence of PI3K decreases D-serine availability, affecting synaptic plasticity.
The study also links glucose metabolism to memory. The lack of PI3K in astrocytes reduces glucose uptake, which not only provides energy but also serves as a raw material for L-serine. This metabolic alteration triggers a cascade of effects that negatively impact memory formation.
Administering L-serine in the mice's diet proved effective. Over several weeks, the treatment increased serine levels in the brain and restored the animals' performance in spatial memory tests, demonstrating the direct influence of astrocyte metabolism on neuronal and cognitive function.
While the results are promising, researchers caution that this is a study in mice and does not yet allow for direct conclusions in humans. The work redefines the understanding of memory, showing it depends not only on neurons and their connections but also on the activity and metabolism of surrounding cells. This knowledge opens avenues for investigating cognitive disorders and learning mechanisms.
