Abstract

The applicant proposes to measure changes in the size and number of neurons and their dendrites and axons in the TThC in his transgenic mice. To determine the mechanisms by which IGF-I influences neural development, he will examine IGF-I's in vivo effects on a) neuronal cell proliferation and migration, b) neuronal apoptosis, c) the regulation of type I receptors and d) the expression of candidate genes that may mediate the changes induced by IGF-I. The modulatory effects of IGFBPs will also be studied using primary neuronal studies. Finally, the applicant will test the hypothesis that decreases in IGF-I expression or actions mediate the brain pathology of malnutrition. He predicts that IGF-I overexpression will ameliorate and IGFBP-1 expression will exacerbate malnutrition's effects on the TThC.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD008299-25
Application #
2673409
Study Section
Endocrinology Study Section (END)
Project Start
1977-06-01
Project End
2000-05-31
Budget Start
1998-06-01
Budget End
1999-05-31
Support Year
25
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Pediatrics
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Hu, Qichen; Lee, Seong Yong; O'Kusky, John R et al. (2012) Signalling through the type 1 insulin-like growth factor receptor (IGF1R) interacts with canonical Wnt signalling to promote neural proliferation in developing brain. ASN Neuro 4:
Liu, Wen; D'Ercole, Joseph A; Ye, Ping (2011) Blunting type 1 insulin-like growth factor receptor expression exacerbates neuronal apoptosis following hypoxic/ischemic injury. BMC Neurosci 12:64
Lehtinen, Maria K; Zappaterra, Mauro W; Chen, Xi et al. (2011) The cerebrospinal fluid provides a proliferative niche for neural progenitor cells. Neuron 69:893-905
Ye, Ping; Hu, Qichen; Liu, Hedi et al. (2010) beta-catenin mediates insulin-like growth factor-I actions to promote cyclin D1 mRNA expression, cell proliferation and survival in oligodendroglial cultures. Glia 58:1031-41
Moy, S S; Nadler, J J; Young, N B et al. (2009) Social approach in genetically engineered mouse lines relevant to autism. Genes Brain Behav 8:129-42
Liu, Wen; Ye, Ping; O'Kusky, John R et al. (2009) Type 1 insulin-like growth factor receptor signaling is essential for the development of the hippocampal formation and dentate gyrus. J Neurosci Res 87:2821-32
Joseph D'Ercole, A; Ye, Ping (2008) Expanding the mind: insulin-like growth factor I and brain development. Endocrinology 149:5958-62
Zhang, Jihui; Moats-Staats, Billie M; Ye, Ping et al. (2007) Expression of insulin-like growth factor system genes during the early postnatal neurogenesis in the mouse hippocampus. J Neurosci Res 85:1618-27
Zhang, Jihui; Liu, Wen; Ye, Ping et al. (2007) Pitfalls of PCR-based strategy for genotyping cre-loxP mice. Biotechniques 42:281, 283
Simmons, J G; Ling, Y; Wilkins, H et al. (2007) Cell-specific effects of insulin receptor substrate-1 deficiency on normal and IGF-I-mediated colon growth. Am J Physiol Gastrointest Liver Physiol 293:G995-1003

Showing the most recent 10 out of 104 publications