Astrocyte-specific overexpression of insulin-like growth factor-I promotes brain overgrowth and glial fibrillary acidic protein expression.

Abstract

Insulin-like growth factor-I (IGF-I) is widely expressed in the central nervous system (CNS). Whereas during normal development IGF-I is expressed predominantly by neurons and to a much lesser degree by glial cells, its expression in astrocytes, and often in microglia, is increased during and/or after variety of CNS injuries. Recently we have generated a new line of IGF-I Tg mice, called IGF-I(Ast/Tet-Off) Tg mice, in which IGF-I transgene is expressed specifically in astrocytes and is tightly controlled by the tetracycline analog doxycycline. In this study we examined whether IGF-I derived from astrocytes is capable of promoting neural cell growth during development. When the IGF-I transgene is allowed to be expressed, IGF-I(Ast/Tet-Off) Tg mice exhibit markedly increases in 1) brain weight; 2) brain DNA and protein abundance; and 3) number of neurons, oligodendrocytes, and astrocytes, as well as myelination, findings similar to those observed in our other lines of Tg mice that express IGF-I transgene predominantly in neurons. Unlike Tg mice with neuron-specific IGF-I expression, which manifest marked increases in the concentrations of oligodendrocyte/myelin-specific proteins, however, IGF-I(Ast/Tet-Off) Tg mice exhibit an increase in the concentration of glial fibrillary acidic protein, an astrocyte-specific protein. Furthermore, when transgene expression is blunted, brain overgrowth in IGF-I(Ast/Tet-Off) Tg mice ceases. Our data indicate that astrocyte-derived IGF-I is capable of promoting neural cells growth in vivo. Our data also suggest that IGF-I's actions in CNS depend in part on the location of its expression and cellular microenvironment and that continuous presence of IGF-I expression is necessary for brain overgrowth.

• Authors: Ping Ye, Greg J Popken, April Kemper, Ken McCarthy, Brian Popko, A Joseph D'Ercole
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 78 Issue 4 Pg. 472-84 (Nov 15 2004) ISSN: 0360-4012 [Print] United States
• PMID: 15468174 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Glial Fibrillary Acidic Protein
• RNA, Messenger
• Vimentin
• Insulin-Like Growth Factor I
• Doxycycline

Topics

• Age Factors
• Animals
• Astrocytes (metabolism)
• Blotting, Northern (methods)
• Blotting, Western (methods)
• Body Weight
• Brain (anatomy & histology, cytology, growth & development)
• Cell Count (methods)
• Doxycycline (pharmacology)
• Gene Expression Regulation (drug effects, physiology)
• Glial Fibrillary Acidic Protein (genetics, metabolism)
• Immunohistochemistry (methods)
• In Situ Hybridization (methods)
• Insulin-Like Growth Factor I (genetics, metabolism, physiology)
• Mice
• Mice, Transgenic (physiology)
• Neurons (metabolism)
• Oligodendroglia (metabolism)
• Organ Size (physiology)
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction (methods)
• Vimentin (metabolism)