Brain atlas of 23 macaques identifies brainstem white matter as particularly vulnerable to age-related changes

Brain atlas of 23 macaques identifies brainstem white matter as particularly vulnerable to age-related changes

On August 18, Cell published a study mapping eight brain regions in 23 female cynomolgus macaques. The authors collected 2 955 873 cell nuclei and examined how age-related changes varied across brain regions and cell types.

Aging does not affect all brain regions and cell types in the same way. To characterize these differences, the team compared eight brain regions from macaques of different ages. The researchers created two maps. One used RNA to show gene activity, while the other showed which regions of DNA were accessible to proteins that regulate gene activity. Comparing these maps across brain regions and cell types revealed where age-related changes occurred in several cell lineages.

The most consistent age-related changes occurred in the pons and medulla oblongata, which are regions of the brainstem. Their white matter contains bundles of nerve fibers covered with myelin, a sheath that increases the speed of signal transmission. Oligodendrocytes produce myelin.

In oligodendrocytes from this area, the activity of genes involved in myelin formation and the synthesis of lipids for the myelin sheath declined with age. Signaling also changed in cells that support nervous tissue or give rise to oligodendrocytes. In brain sections, the authors confirmed that RNA expression of the PDGFRA gene decreased in oligodendrocyte precursor cells. This gene encodes a receptor for growth signals. The authors identified the pons and medulla oblongata as a focus of aging in the primate brain because the changes affected several cell lineages.

For the prefrontal cortex, the authors compared the macaque data with human datasets. Some changes in genes involved in synaptic function and protein folding were shared by aging macaques and humans. The overlap was smaller in Alzheimer’s disease, and some programs changed in the opposite direction. This comparison distinguishes age-related changes shared among primates from changes specific to a particular brain region and model.

Processed data from the atlas are available through the NHPABC portal. Users can search for age-related changes by brain region, cell type, and myelin-related program.