Scientists at the Université Paris-Saclay and Université de Bordeaux neuroscience labs have shown a metabolic pathway that plays a decisive role in Alzheimer’s memory problems and shows that the delivery of an amino acid {as a dietary supplement) to an Alzheimer’s mouse model early.
For the brain to function properly, neurons and surrounding cells, especially astrocytes, must work together. The early phase of Alzheimer’s disease is characterized by a decrease in this energy metabolism but this deficit was not known to contribute to Alzheimer’s cognitive symptoms.
A study in an Alzheimer’s mouse model showed that a decrease in astrocyte glucose utilization reduces L-serine production. This amino acid is mainly produced by these brain cells and its biosynthesis process is altered in patients. L-serine is a precursor of D-serine which stimulates NMDA receptors, essential for brain function and memory creation. Therefore, with the production of less L-serine, astrocytes induce reduced activity at these receptors, which alters neuronal plasticity and associated memory abilities. Scientists have shown that memory functions in mice were restored by L-serine.
The alteration of aerobic glycolysis in the brain is often observed early in Alzheimer’s disease (AD). Whether and how this metabolic dysfunction contributes to both synaptic plasticity and behavioral deficits in AD is not known. The biosynthesis pathway in L-serine astrocytes, a glycolysis precursor and d-serine precursor {a synaptic agonist NMDARs receptors required for synaptic plasticity; attenuated in patients with AD. AD mice show lower NMDAR completeness, synaptic deficits, and defective behavior. Similar deficits are observed in hippocampal astrocytes. Dietary supplementation with l-serine prevents both synaptic and behavioral deficits in AD mice. The findings reveal that astrocytic glycolysis controls cognitive functions.
Recognizing the role of L-serine in memory disorders and the efficacy of dietary supplementation, new strategies are emerging in the medical care of Alzheimer’s disease and other metabolic deficits, such as Parkinson’s and Huntington’s. As L-serine is available as a dietary supplement, this compound should be tested in humans through controlled clinical trials.
SOURCE: Cell Metabolism March 2020
