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Investigating the role of diazepam binding inhibitor (DBI) in astrocytes and neural circuit maturation

Award Number: F32NS129591
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 02/01/2023
PERIOD OF PERFORMANCE END DATE: 09/30/2025

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Investigating the role of diazepam binding inhibitor (DBI) in astrocytes and neural circuit maturation - PROJECT SUMMARY Astrocytes are evolutionarily conserved glial cells in the central nervous system (CNS) that play a crucial role in neuronal circuit development and function. Mature astrocytes exhibit remarkably ramified and complex morphology and closely associate with neuronal synapses throughout the brain. Diazepam binding inhibitor (DBI) is a protein that has been shown to be highly enriched in glial cells, including astrocytes, in mouse and human brains. We recently discovered that it is also highly expressed by Drosophila astrocytes, suggesting its crucial and evolutionarily conserved role in astrocyte function. DBI and its proteolytic neuropeptide, Octadecaneuropeptide (ODN), have been shown to bind to the benzodiazepine (BZD) binding site on GABAA receptors and modulate the strength of inhibitory signaling, acting as endogenous ligands of BZD (endozepines). As BZDs are among the most widely prescribed treatments for anxiety disorders and seizures, understanding the astrocytic endozepine signaling will provide insights into how astrocytes can regulate the proper maturation and function of neuronal circuitry, and how the brain responds to BDZs. Another proteolytic fragment of DBI, triakontatetraneuropeptide (TTN), binds to translocator protein (TSPO) receptor on the outer mitochondrial membrane and is involved in mitochondrial cholesterol transport, cytoskeletal dynamics, and Ca2+ homeostasis, all of which are critical for astrocyte morphogenesis and function. Employing a synergistic combination of molecular-genetic tools available in Drosophila and zebrafish, this proposal aims to: determine whether DBI signaling is required for normal astrocyte development (Aim 1); define cell-intrinsic function of TTN-TSPO signaling in astrocyte mitochondrial and Ca2+ dynamics (Aim 2); and investigate the role of astrocytic DBI signaling in neuronal circuit maturation in the context of the excitatory- inhibitory (E/I) balance. This work will elucidate evolutionarily conserved function of DBI signaling in astrocyte development and astrocyte-neuron interactions in vivo and could provide novel insights into the role of astrocytes in anxiety disorders and epilepsy.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $55,304 )
2025	2025	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/14/2025	NON-COMPETING CONTINUATION	$55,304
														Subtotal = $55,304

Issue Date FY: 2024 ( Subtotal = $74,284 )
2024	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	5/8/2024	NON-COMPETING CONTINUATION	$4,784
2024	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/25/2024	NON-COMPETING CONTINUATION	$69,500
														Subtotal = $74,284

Issue Date FY: 2023 ( Subtotal = $69,080 )
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	1	1/25/2023	NEW	$0
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	005	1	2/17/2023	NEW	$0
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	1	12/23/2022	NEW	$0
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	1	2/9/2023	NEW	$1,906
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	12/23/2022	NEW	$0
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/23/2022	NEW	$67,174
														Subtotal = $69,080

Grand Total All Awards = $198,668

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Investigating the role of diazepam binding inhibitor (DBI) in astrocytes and neural circuit maturation

Award Number: F32NS129591

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 02/01/2023

PERIOD OF PERFORMANCE END DATE: 09/30/2025

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