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The Role of Microglia in Adolescent Ethanol-Induced Corticolimbic Damage

Award Number: F32AA029928
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 03/01/2022
PERIOD OF PERFORMANCE END DATE: 06/11/2023

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The Role of Microglia in Adolescent Ethanol-Induced Corticolimbic Damage - Project Summary Excess alcohol use in adolescence is associated with negative health consequences including corticolimbic damage and cognitive deficits. However, the mechanisms underlying these negative sequelae are not well understood. Microglia, macrophages that reside within the brain, are activated in both humans and animals exposed to alcohol. Activation of microglia to a proinflammatory phenotype can lead to tissue damage and is thus considered a possible cause of adolescent corticolimbic damage following ethanol exposure. Interestingly, we do not see evidence of a proinflammatory microglial phenotype concomitant with corticolimbic pathology in binge ethanol exposed rats. Given that microglial function is more complex than previously appreciated, we consider instead that microglia may serve a neuroprotective role following exposure to ethanol. To test this hypothesis in Aim 1 adolescent rats will be exposed to 2 days of binge ethanol following by microglial morphological and transcriptomic analysis to characterize activation state. Microglia will then be depleted prior to, throughout, and following ethanol exposure using a CSF1R antagonist to determine the effects on markers of neurodegeneration and cognitive function. Interestingly, microglia are known to exhibit a form of immune memory by which prior exposure results in altered responsivity to future activation. We hypothesize that persistent changes to the microglial set-point underlie exacerbation of corticolimbic pathology with repeat exposure to ethanol. In Aim 2 adolescent rats will undergo 2 days of binge ethanol exposure followed by microglia depletion and repopulation before another 2 days of binge ethanol exposure. This replacement of the microglia population may serve to reset these cells to a baseline phenotype. We expect (1) that rats exposed to both ethanol binges will show greater microglial activation, corticolimbic neurodegeneration and cognitive deficits relative to a single 2-day binge ethanol exposure, and (2) that forced microglia turnover will ameliorate these effects. In combination, these aims will significantly enhance our understanding of role that microglial activation and memory play in corticolimbic neurodegeneration following exposure to ethanol.


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: 2024 ( Subtotal = -$4,075 )
2024	2023	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Alcohol Research Programs	000	2	4/24/2024	NON-COMPETING CONTINUATION	-$4,075
														Subtotal = -$4,075

Issue Date FY: 2023 ( Subtotal = $23,374 )
2023	2023	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Alcohol Research Programs	000	2	2/8/2023	NON-COMPETING CONTINUATION	$73,772
2023	2023	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Alcohol Research Programs	001	2	6/30/2023	NON-COMPETING CONTINUATION	-$50,398
														Subtotal = $23,374

Issue Date FY: 2021 ( Subtotal = $66,390 )
2021	2021	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Alcohol Research Programs	000	1	9/7/2021	NEW	$66,390
2021	2021	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Alcohol Research Programs	001	1	9/7/2021	NEW	$0
														Subtotal = $66,390

Grand Total All Awards = $85,689

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The Role of Microglia in Adolescent Ethanol-Induced Corticolimbic Damage

Award Number: F32AA029928

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 03/01/2022

PERIOD OF PERFORMANCE END DATE: 06/11/2023

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