Astrocyte Heterogeneity, Development and Function in Brain Regions Relevant to Mental Illness
NAMHC Concept Clearance:
David M. Panchision, Ph.D.
Chief, Developmental Neurobiology Program
Molecular, Cellular, and Genomic Research Branch
Division of Neuroscience and Basic Behavioral Science (DNBBS)
This initiative will support discovery research on astrocyte diversity and function, adaptation of new technologies to astrocyte research, and the application of these to the study of brain processes relevant to mental illness.
It is estimated that 50 percent of human brain mass is composed of astrocytes, which have protracted courses of development that correlate with the trajectory of mental illnesses. There is increasing evidence linking astrocytes to mental illnesses. For example, astrocytes are enriched in serine metabolic enzymes linked to schizophrenia, and astrocyte abnormalities are found in post-mortem studies of individuals with schizophrenia, suggesting a causal role. However, most basic neuroscience funding and studies focus on neurons, while studies of astrocytes are relatively few in number. This gap has been due to the lack of tools to identify and target astrocytes robustly. However, a convergence of new astrocyte markers and genetic tools to study astrocyte function provide traction to address this gap, and to yield mechanisms or predictive measures of glial function relevant to mental illness.
This initiative will support discovery-based research on astrocytes in three areas:
- Defining the molecular basis of functional heterogeneity between astrocyte subtypes in the brain;
- Developing or utilizing new genetic tools for reporting or manipulating astrocyte development, subtype identity, or function; and,
- Using these novel tools or subtype properties to assay brain regions or domains of function relevant to mental illnesses.
We expect this research will:
- Yield new tools for reporting and manipulating diverse astrocyte subtypes in model systems;
- Characterize novel combinatorial regulatory mechanisms of astrocyte development;
- Identify mechanisms by which astrocytes regulate neural circuits serving cognition, emotion or social function;
- Distinguish the role of astrocytes in gene variants or gene-environment-development interactions relevant to mental illnesses; and,
- Indicate new astrocyte activities that may be therapeutic targets for mental illnesses.