Astroglia heterogeneity in the adult central nervous system in health and disease

Astroglia are essential for the homeostasis and maintenance of the central nervous system (CNS). They are the most abundant neuroglia cell type and display a vast array of roles such as: neurotransmitter regulation, neurotrophic release, immune signaling, blood-brain-barrier maintenance, ion buffering, release of gliotransmitters, and neurotoxin secretion. It is not surprising that astroglia in different regions display diverse functions in order to maintain their environmental niche. Historically, astroglia were placed into two groups based on their neuroanatomical localization and morphological depictions: protoplasmic astroglia of the grey matter and fibrous astroglia of the white matter. However, recent accumulating evidence has suggested that astroglia consist of many different subpopulations, similar to neuronal heterogeneity. Unfortunately, there still remain large gaps in our understanding of these different subtypes due to a lack of molecular markers to identify and study these populations. In this study, we generated a novel transgenic mouse model that selectively and robustly labels one specific astroglia subpopulation in the adult CNS. We show that this astrocyte population regulates neuronal spine density and dendritic branching in cortical layers II/III and V. Furthermore, we show that this astrocyte subpopulation is dramatically affected in amyotrophic lateral sclerosis. Taken together, these findings provide a marker for further study of this newly identified astrocyte subpopulation in both health and disease, including the potential to generate cell subtype-specific therapeutics for several neurological disorders