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Immune mechanisms underlying sex-specific adolescent periods of vulnerability for social dysfunction in aging

Award Number: R03AG070111
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2020
PERIOD OF PERFORMANCE END DATE: 05/31/2023

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Immune mechanisms underlying sex-specific adolescent periods of vulnerability for social dysfunction in aging - PROJECT SUMMARY Social networks and support are integral to health and wellness across the lifespan, and social engagement may be particularly important to preserve overall health and cognitive function during aging. However, social behavior and social cognition decline during aging. A better understanding of the neural mechanisms underlying healthy and abnormal social behaviors is fundamental to increasing healthy aging outcomes. Social behaviors are supported by the ‘reward’ circuitry, a network of brain regions that develops during adolescence. We have shown that microglia, the resident immune cells of the brain, play a crucial role in reward circuitry and social behavior development in adolescent rats. Microglia phagocytose and eliminate, or ‘prune’, synaptic receptors in the nucleus accumbens (NAc) reward region between pre-early adolescence in females, and between early-mid adolescence in males. Interfering with microglia-mediated NAc pruning during each sex- specific pruning stage altered social behavior development in both sexes. In this proposal, we will determine how healthy and abnormal immune signaling in the NAc during adolescence sex-specifically shapes social behavior across the lifespan. Specifically, we will determine whether (1) interfering with NAc pruning in adolescent male and female rats increases social behaviors across the lifespan, (2) social stress during adolescence, a pro-inflammatory stimulus that impairs reward circuitry and social behavior development, exacerbates microglial pruning in the NAc, and (3) social stress during adolescence worsens aging-related social behavior dysfunction. Our core hypothesis is that healthy microglia- mediated pruning in the NAc during adolescence supports social behavior throughout the lifespan, and that the sex-specific developmental stages during which NAc pruning occurs will thus constitute sex-specific periods of vulnerability for life long social abnormalities. These studies treat developmental stage and sex as independent variables to advance our understanding of how healthy and abnormal adolescent development in the NAc impacts social behavior and neuro-immune signaling across the lifespan. The successful completion of this proposal will produce novel insights regarding the impact of aberrant sex-specific developmental mechanisms during adolescence that may be important for healthy aging outcomes.


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 = $0 )
2024	2021	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE # A34	ALBANY	NY	12208	ALBANY	USA	Aging Research	000	2	1/16/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $163,000 )
2021	2021	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Aging Research	000	2	4/26/2021	NON-COMPETING CONTINUATION	$163,000
														Subtotal = $163,000

Issue Date FY: 2020 ( Subtotal = $162,833 )
2020	2020	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Aging Research	000	1	9/18/2020	NEW	$162,833
														Subtotal = $162,833

Grand Total All Awards = $325,833

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Immune mechanisms underlying sex-specific adolescent periods of vulnerability for social dysfunction in aging

Award Number: R03AG070111

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/30/2020

PERIOD OF PERFORMANCE END DATE: 05/31/2023

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