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IGF-1 IN NEOCORTICAL DEVELOPMENT AND PLASTICITY

Award Number: R01NS046008
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: HEALTH SERVICES
PERIOD OF PERFORMANCE START DATE: 03/01/2003
PERIOD OF PERFORMANCE END DATE: 02/28/2007

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IGF-1 IN NEOCORTICAL DEVELOPMENT AND PLASTICITY - DESCRIPTION (provided by applicant): Understanding the regulation of dendritic growth is essential to understanding how neural circuits form and function. Dendrites are the targets of 90% of all synapses, and both the extent and pattern of dendritic branching critically influence the integration of synaptic inputs. The cognitive impairments that accompany many developmental disorders are likely to result in part from inappropriate regulation of dendritic growth and plasticity in the developing CNS. One significant challenge currently is elucidating the molecular mediators that control of how much and where dendrites elaborate during development. Recent evidence suggests that neural activity influences dendritic growth through the actions of trophic factors, which focally promote formation and elaboration of new branches. It is likely, however, that one or more factors promote dendritic elaboration more generally and thereby prime neurons for the focal regulation of development and plasticity that is mediated by factors with more restricted actions. With respect to agents that might provide a broad but critical stimulus for dendritic elaboration, insulin-like growth factor 1 (IGF-1) is of particular interest. IGF receptors are widely expressed in the developing brain. IGF-1 can cross from the plasma into the brain as an endocrine factor, and also may act in a paracrine and/or autocrine fashion following production by cells of the cerebral vasculature and by neurons and glia within the brain. Several laboratories have reported that IGF-1 promotes dendritic elaboration by neurons in vitro. Moreover, the growth of neuropil in the cerebral cortex appears to be increased in transgenic mice in which IGF-1 is overexpressed and decreased in mice in which IGF-1 activity is decreased. Significantly, human studies and clinical cases indicate that abnormal IGF-1 signaling during development can result in intellectual impairment, which may arise in part from dysregulation of dendritic development. Building upon such studies, the experiments proposed will test key predictions of the hypothesis that IGF-1 modulates the growth of neuropil and provides a critical stimulus for dendritic elaboration in the developing cerebral cortex. IGF-1-dependent regulation of dendritic development will be tested in vitro, using organotypic slices of the developing cerebral cortex, and also in vivo, using transgenic mice in which IGF-1 signaling is increased or decreased specifically within the brain.


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: 2006 ( Subtotal = $266,243 )
2006	2006	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	2/28/2006	NON-COMPETING CONTINUATION	$266,243
														Subtotal = $266,243

Issue Date FY: 2005 ( Subtotal = $272,650 )
2005	2005	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/22/2005	NON-COMPETING CONTINUATION	$272,650
														Subtotal = $272,650

Issue Date FY: 2004 ( Subtotal = $272,888 )
2004	2004	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	2/26/2004	NON-COMPETING CONTINUATION	$272,888
														Subtotal = $272,888

Issue Date FY: 2003 ( Subtotal = $297,350 )
2003	2003	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1		NEW	$297,350
														Subtotal = $297,350

Grand Total All Awards = $1,109,131

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IGF-1 IN NEOCORTICAL DEVELOPMENT AND PLASTICITY

Award Number: R01NS046008

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: HEALTH SERVICES

PERIOD OF PERFORMANCE START DATE: 03/01/2003

PERIOD OF PERFORMANCE END DATE: 02/28/2007

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