Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. ABSTRACT Recent studies indicate that astrocytes are spatially diversified, which may have consequence for psychiatric diseases with regional brain dysfunction. However, establishing diversified functions of astrocytes in brain development and disease has been limited by a lack of tools for lineage-specific astrocyte manipulation. Recently, we developed novel transgenic methods to label, purify and characterize regional astrocyte populations in mouse brain. The midbrain and brainstem contain dopaminergic nuclei of the ventral tegmental area (VTA) and substantia nigra (SN) that are implicated in schizophrenia, ADHD and Parkinson's disease. We will test the hypothesis that regionally-specified astrocytes from the ventral midbrain are uniquely suited to support survival and connectivity of dopaminergic projections from the VTA and SN. We will determine molecular diversity of region-restricted midbrain astrocytes as a first step towards uncovering the role of regionally diverse astrocytes in neurological disorders. Deliverables include validated transgenic mouse tools for conditional temporal- spatial labeling, purification of astrocytes throughout the CNS as well as markers of regionally heterogeneous astrocytes subtypes of mid/hindbrain compiled into a public database. The project is intended to reveal signatures of astrocyte subtypes and provide insight into the role of astrocytes in mental health.

Public Health Relevance

The role of astrocytes in brain function and dysfunction remains one of the great unknowns in neurobiology. The major objective of this proposal is to develop these tools to more clearly define astrocyte diversity and function in midbrain dopaminergic neuron survival and axon path finding. Upon successful completion of these studies we will have a clearer understanding of astrocyte diversity and function and their potential roles in human psychiatric disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH099595-02
Application #
8600322
Study Section
Special Emphasis Panel (ZMH1-ERB-M (06))
Program Officer
Panchision, David M
Project Start
2012-12-20
Project End
2015-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
2
Fiscal Year
2014
Total Cost
$247,932
Indirect Cost
$90,432
Name
University of California San Francisco
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Molofsky, Anna V; Kelley, Kevin W; Tsai, Hui-Hsin et al. (2014) Astrocyte-encoded positional cues maintain sensorimotor circuit integrity. Nature 509:189-94
Molofsky, Anna V; Glasgow, Stacey M; Chaboub, Lesley S et al. (2013) Expression profiling of Aldh1l1-precursors in the developing spinal cord reveals glial lineage-specific genes and direct Sox9-Nfe2l1 interactions. Glia 61:1518-32