Astrocyte-specific overexpression of insulin-like growth factor-I promotes brain overgrowth and glial fibrillary acidic protein expression
Article first published online: 5 OCT 2004
Copyright © 2004 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 78, Issue 4, pages 472–484, 15 November 2004
How to Cite
Ye, P., Popken, G. J., Kemper, A., McCarthy, K., Popko, B. and D'Ercole, A. J. (2004), Astrocyte-specific overexpression of insulin-like growth factor-I promotes brain overgrowth and glial fibrillary acidic protein expression. J. Neurosci. Res., 78: 472–484. doi: 10.1002/jnr.20288
- Issue published online: 21 OCT 2004
- Article first published online: 5 OCT 2004
- Manuscript Accepted: 30 JUL 2004
- Manuscript Revised: 28 JUL 2004
- Manuscript Received: 11 JUN 2004
- National Institutes of Health. Grant Numbers: NS38891, HD08299, NS34939, RG3291-A-4
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-IAst/Tet-OffTg 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-IAst/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-IAst/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-IAst/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.