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The role of intermittent binge ethanol, sex, and age on memory and CREB binding protein (CBP) expression

Award Number: F31AA029305
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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Summary In humans, adolescence is a critical developmental period marked by increased risk-taking behaviors, brain maturation, and cognitive development. Alcohol is highly consumed as an easy drug for most underage drinkers to obtain. The early age of drinking increases one’s risk of alcohol abuse and dependence later in life and can lead to lasting changes in protein expression and behavior. Adolescents have an altered sensitivity to alcohol likely due to their ongoing development, showing decreased sensitivity to the negative effects while having increased sensitivity to the rewarding effects as compared to adults. This difference in development may further promote alcohol drinking in adolescents, resulting in long-lasting changes that are more severe than in adults. Alcohol consumption has resulted in changes in protein expression and memory impairments observed in both adults and adolescents. Two known proteins involved in memory are cAMP-response element binding (CREB) protein and CREB binding protein (CBP). CBP is a histone acetyltransferase, coactivator/cofactor for many transcription factors including CREB, and necessary for both short term and long- term memory. The hippocampus and prefrontal cortex are two brain regions that undergo maturation changes during adolescence and play a role in memory. Sex is also known to play a role in memory and studies have suggested women may be more sensitive to the effects of alcohol. Given the lasting impact alcohol can have on behavior and the brain, further understanding the persistent effects of alcohol due to sex and age is important for the literature and further treatment possibilities. Our lab has shown ethanol to differentially impact memory 3 weeks after the last dose, with an observed deficit in the novel object recognition task in adolescent treated mice but not adult treated mice. Furthermore, we found several genes related to CRE, CREB, and CBP were decreased due to ethanol following microarray analysis. This proposal will investigate the effects of sex, ethanol, and developmental age on memory and CBP protein expression using behavioral and molecular assays in DBA/2J mice. Aim 1 will investigate the impact of binge ethanol on ethanol metabolism, spatial memory, and cognitive flexibility in male and female mice treated with ethanol in adolescence and adulthood using blood ethanol concentration and the Barnes Maze task. In Aim 2, I will assess the level of protein expression of CBP and other proteins that interact with CBP or are involved with CRE/CREB using westerns. I will also assess CBP protein interactions using co-immunoprecipitation coupled with mass spectrometry. Finally, in Aim 3 I will test the sufficiency of CBP using viral vectors in mice following the adolescent binge ethanol procedure to assess the impact on the previously mentioned memory tasks. The combination of these behavioral and molecular studies will provide useful knowledge to the literature addressing the gap regarding developmental age, sex, and ethanol in memory and the CBP pathway.


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: 2023 ( Subtotal = $41,294 )
2023	2023	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Alcohol Research Programs	000	3	4/12/2023	NON-COMPETING CONTINUATION	$41,294
														Subtotal = $41,294

Issue Date FY: 2022 ( Subtotal = $40,352 )
2022	2022	VIRGINIA COMMONWEALTH UNIVERSITY	912 W FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Alcohol Research Programs	001	2	5/24/2022	NON-COMPETING CONTINUATION	-$1
2022	2022	VIRGINIA COMMONWEALTH UNIVERSITY	912 W FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Alcohol Research Programs	000	2	5/5/2022	NON-COMPETING CONTINUATION	$40,353
														Subtotal = $40,352

Issue Date FY: 2021 ( Subtotal = $39,636 )
2021	2021	VIRGINIA COMMONWEALTH UNIVERSITY	912 W FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Alcohol Research Programs	000	1	6/9/2021	NEW	$39,636
2021	2021	VIRGINIA COMMONWEALTH UNIVERSITY	912 W FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Alcohol Research Programs	001	1	6/9/2021	NEW	$0
														Subtotal = $39,636

Grand Total All Awards = $121,282

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The role of intermittent binge ethanol, sex, and age on memory and CREB binding protein (CBP) expression

Award Number: F31AA029305

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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