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

Abstract

Astrocytes are a subtype of glial cells, which are non-neuronal cells that do not produce electrical impulses. 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. While in the past astrocytes were mostly examined in rodents, it is now clear that there is a large amount of astrocyte heterogeneity and increased complexity in mammals and primates (Oberheim et al. 2009; Falcone et al. 2019; Falcone et al. 2021; Falcone and Martinez-Cerdeno 2023). Astrocytes have expanded in the human lineage (density, soma volume, and 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. What are the underlying changes in astrocytes in primate evolution? For this review, we will focus on gene expression evolution 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 (iPSCs) and single-cell RNA sequencing (scRNA-Seq). Furthermore, understanding the evolution of astrocytes across primates will help to 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.