Exploring the Expanded Role of Astrocytes in Primate Brain Evolution via Changes in Gene Expression

Background: Astrocytes are a subtype of glial cells, which are non-neuronal cells that do not produce action potentials. Rather, astrocytes are involved in various functions vital to a functioning brain including nutrient supply to neuronal cells, blood-brain barrier maintenance, regulation of synaptic transmission, and repair following CNS injury. Summary: While astrocytes have been examined extensively in rodents, it is now clear that there is a large amount of astrocyte heterogeneity and increased complexity in mammals and primates. Astrocytes have expanded in the human lineage with respect to density, soma volume, and the ratio of astrocytes to total glial cells. The human prefrontal cortex also possesses an overall increased glia:neuron ratio relative to other primates, coinciding with allometric expectations based on overall brain size. Key Messages: What are the underlying changes in astrocytes in primate evolution? For this review, we will focus on the evolution of gene expression and gene regulation in astrocytes as a read out of the phenotypic changes seen in cellular morphology. This is an exciting time to understand this cell type in a more dynamic and complex way with new technologies such as induced pluripotent stem cells and single-cell RNA sequencing. Furthermore, understanding the evolution of astrocytes across primates will help explain their role in neurological disease as alterations in astrocyte function are implicated in many neurodegenerative states such as Alzheimer’s disease and Parkinson’s disease.