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

✍ Scribed by Ping Ye; Greg J. Popken; April Kemper; Ken McCarthy; Brian Popko; A. Joseph D'Ercole

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 572 KB
• Volume: 78
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.20288

✦ Synopsis

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 predominately 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 predominately 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. © 2004 Wiley‐Liss, Inc.