Brain enzyme in stem cells drives cognitive aging in mice
As the brain ages, key connections between nerve cells start to malfunction. Researchers have now identified an enzyme that contributes to this decline in mice, and suppressing it improved cognitive performance. The findings were published in Nature Aging.
The enzyme is called PLA2G7 and is produced by stem cells in the hippocampus (the brain region central to learning and memory). In older mice, these stem cells overproduce PLA2G7. This excess negatively affects inhibitory synapses (the connection points between nerve cells that dampen the activity of other neurons). When inhibitory synapses work less effectively, cognitive function declines. The study found that suppressing PLA2G7 in neural stem cells improved synaptic transmission and measurably boosted cognitive performance in aged mice.
Hippocampal stem cells as a target
The hippocampus is one of the brain regions most visibly affected by aging. Stem cells there generate new neurons, but their behavior changes with age. PLA2G7, an enzyme that breaks down fatty acids, acts as a negative regulator of inhibitory synapses. In practical terms: more PLA2G7 leads to less effective inhibitory signaling in the circuit, which is associated with poorer cognition.
By suppressing PLA2G7, the team improved synaptic transmission in the dentate gyrus, a subregion of the hippocampus involved in distinguishing new information from familiar experiences. Aged mice subsequently performed better on cognitive tasks.
Preliminary findings in mice
This study was conducted in mice. Whether the same mechanism operates in humans, and whether PLA2G7 is a viable therapeutic target, has not yet been investigated. The researchers suggest that stem cell-related changes in the hippocampus contribute to cognitive decline during aging, but further studies are needed to confirm this.
The intervention targeted stem cells rather than neurons directly. Whether that offers a broader advantage for early intervention in aging remains an open question not addressed by this study.
Want to research this yourself?
Search for example:
- PLA2G7 hippocampus aging
- inhibitory synapse dentate gyrus
- neural stem cell cognition