MBOAT2 and lipids from young cells helped old mouse neural stem cells exit quiescence

MBOAT2 and lipids from young cells helped old mouse neural stem cells exit quiescence

On July 29, Science Advances published a study of quiescent neural stem cells from young and old mice. The authors examined how age-related changes in plasma membrane lipids affect the activation of these cells, focusing on the enzyme MBOAT2 and lipids from young cells.

In the adult brain, neural stem cells usually remain quiescent until they receive a signal to divide. Once activated, they begin producing progenitor cells, which give rise to new cells in nervous tissue. This transition becomes less frequent with age. Xiaoai Zhao's team investigated whether the cell membrane contributes to this decline. The plasma membrane separates the cell from its environment, and its lipids determine the properties of this barrier.

The membrane consists of lipids, molecules that form its bilayer. The lipid composition affects how orderly this bilayer is. The authors compared cells from young and old mice, then tested some of their findings in freshly isolated cells and brain slices. Specific complex lipids were altered in old quiescent cells, and the lipid layer became less ordered.

The authors then examined the mechanism. Mboat2 encodes MBOAT2, an enzyme that modifies phospholipid composition. When the researchers disabled this gene in old cells, the age-related lipid changes became more pronounced, and the cells had greater difficulty beginning to divide. Increasing Mboat2 expression shifted some lipids toward the profile found in young cells. It also increased the proportion of old cells that became activated, both in culture and in the mouse brain.

In another experiment, the authors isolated lipids from the plasma membranes of young neural stem cells and added them to old quiescent cells. The old cells then became activated more often. Both increasing Mboat2 expression and adding lipids from young cells restored the ability of old cells to begin dividing.

These experiments in mouse cells and mice indicate that membrane lipid composition joins genes and metabolism as part of the mechanism underlying neural stem cell aging. Regeneration in the aging brain depends not only on signals within the cell, but also on the composition of its membrane.