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GROWTH HORMONE & IGF-1 IN CNS AND CEREBROVASCULAR AGING

Award Number: P01AG011370
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/11/1997
PERIOD OF PERFORMANCE END DATE: 03/31/2013

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GROWTH HORMONE & IGF-1 IN CNS AND CEREBROVASCULAR AGING - DESCRIPTION (provided by applicant): This application is a competing continuation of a Program Project entitled 'Growth Hormone & IGF-1 in CNS and Cerebrovascular Aging'. The project is based on several key findings indicating that the progressive decline in plasma growth hormone and IGF-1 throughout the lifespan not only has an important effect on aging of peripheral tissues but that decreases in the levels of these hormones contribute to a decline in cognitive function. We hypothesize that the age-related cognitive decline results from a loss of growth hormone/IGF-1 dependent factors and/or inability to compensate for such a loss. Our proposed continued investigation into the role of growth hormone and IGF-1 deficiencies on brain aging includes three projects supported by Administration and Animal Cores. Project 1 is based on previously published seminal findings and preliminary studies that plasma growth hormone and IGF-1 are key regulators of vascular density, vascular reactivity and blood flow and hypothesizes that deficiencies in growth hormone and IGF-1 result in a mismatch between blood flow and metabolic demand in specific brain regions. Project 2 focuses on the role of growth hormone/IGF-l in regulating cell turnover in the aging brain and will assess whether the growth hormone/IGF-1 axis is a critical regulator of the replacement of both neurons and glia, sand that deficiency of these hormones result in increased oxidative stress and inflammation resulting in functional decline and a decreased ability to prevent and repair damage in the CNS. Project 3 is based on our findings that subunit levels of NMDA and AMPA types of glutamate receptors decrease with age in the rodent hippocampus and that IGF-1 infusion into the lateral ventricles increases synaptic complexity. Proposed studies will investigate age-related changes in the synaptic distribution of NMDA and AMPA subunits and their association with brain levels of IGF-1. An extremely novel aspect of this application is that the projects will incorporate an animal model of adult-onset growth hormone deficiency. This model will permit us to evaluate the specific actions of growth hormone and IGF-1 apart from pathological or secondary age-related changes within the CNS. The proposed studies will address key questions of the relationship between endocrine and microvascular changes and the neural substrates that contribute to cognitive decline, vascular dementia and increased susceptibility to diseases commonly observed in the elderly, including Alzheimer's disease.


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: 2012 ( Subtotal = $0 )
2012	2010	UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER	POST OFFICE BOX 26901	OKLAHOMA CITY	OK	73190	OKLAHOMA	USA	Aging Research	000	16	3/28/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2010 ( Subtotal = $1,240,365 )
2010	2010	UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER	P.O. BOX 26901	OKLAHOMA CITY	OK	73190	OKLAHOMA	USA	Aging Research	000	16	3/18/2010	NON-COMPETING CONTINUATION	$1,240,365
														Subtotal = $1,240,365

Issue Date FY: 2009 ( Subtotal = $1,256,201 )
2009	2009	UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER	P.O. BOX 26901	OKLAHOMA CITY	OK	73190	OKLAHOMA	USA	Aging Research	001	15	9/11/2009	SUPPLEMENT FOR EXPANSION	$39,802
2009	2009	UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER	P.O. BOX 26901	OKLAHOMA CITY	OK	73190	OKLAHOMA	USA	Aging Research	000	15	3/24/2009	NON-COMPETING CONTINUATION	$1,216,399
														Subtotal = $1,256,201

Issue Date FY: 2008 ( Subtotal = $1,218,068 )
2008	2008	UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER	POST OFFICE BOX 26901	OKLAHOMA CITY	OK	73190	OKLAHOMA	USA	Aging Research	000	14	3/10/2008	NON-COMPETING CONTINUATION	$1,218,068
														Subtotal = $1,218,068

Issue Date FY: 2007 ( Subtotal = $1,203,764 )
2007	2007	UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER	POST OFFICE BOX 26901	OKLAHOMA CITY	OK	73190	OKLAHOMA	USA	Aging Research	001	13	9/24/2007	SUPPLEMENT FOR EXPANSION	$43,245
2007	2007	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	12	3/22/2007	NON-COMPETING CONTINUATION	$247,399
2007	2007	UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER	POST OFFICE BOX 26901	OKLAHOMA CITY	OK	73190	OKLAHOMA	USA	Aging Research	000	13	9/18/2007	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$913,120
														Subtotal = $1,203,764

Issue Date FY: 2006 ( Subtotal = $1,214,734 )
2006	2006	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	11	5/31/2006	COMPETING CONTINUATION	$1,214,734
														Subtotal = $1,214,734

Issue Date FY: 2005 ( Subtotal = $1,070,409 )
2005	2005	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	10	4/4/2005	NON-COMPETING CONTINUATION	$1,070,409
														Subtotal = $1,070,409

Issue Date FY: 2004 ( Subtotal = $1,040,149 )
2004	2004	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	9	3/15/2004	NON-COMPETING CONTINUATION	$1,040,149
														Subtotal = $1,040,149

Issue Date FY: 2003 ( Subtotal = $1,050,507 )
2003	2003	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	8		COMPETING CONTINUATION	$1,050,507
														Subtotal = $1,050,507

Issue Date FY: 2002 ( Subtotal = $51,202 )
2002	2002	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Aging Research	002	7	5/10/2002	SUPPLEMENT FOR EXPANSION	$51,202
														Subtotal = $51,202

Issue Date FY: 2001 ( Subtotal = $751,655 )
2001	2001	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Aging Research	000	7	3/2/2001	NON-COMPETING CONTINUATION	$672,111
2001	2001	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Aging Research	001	7	3/8/2001	SUPPLEMENT FOR EXPANSION	$79,544
														Subtotal = $751,655

Issue Date FY: 2000 ( Subtotal = $641,751 )
2000	2000	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Aging Research	000	6	3/23/2000	NON-COMPETING CONTINUATION	$641,751
														Subtotal = $641,751

Issue Date FY: 1999 ( Subtotal = $620,275 )
1999	1999	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Aging Research	000	5	3/9/1999	NON-COMPETING CONTINUATION	$620,275
														Subtotal = $620,275

Issue Date FY: 1998 ( Subtotal = $604,648 )
1998	1998	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Aging Research	000	4	4/17/1998	COMPETING CONTINUATION	$604,648
														Subtotal = $604,648

Grand Total All Awards = $11,963,728

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GROWTH HORMONE & IGF-1 IN CNS AND CEREBROVASCULAR AGING

Award Number: P01AG011370

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/11/1997

PERIOD OF PERFORMANCE END DATE: 03/31/2013

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