title: IGF-I redirects doublecortin-positive cell migration in the normal adult rat brain.
abstract: The migration of subventricular zone (SVZ)-derived neural precursor cells through the rostral migratory stream (RMS) to the olfactory bulb is tightly regulated by local micro-environmental cues. Insulin-like Growth Factor-I (IGF-I) can stimulate the migration of several neuronal cell types and acts as a 'departure' factor in the avian SVZ. To establish whether IGF-I can also act as a migratory factor for adult neuronal precursor cells in vivo, in addition to its well established role in precursor cell proliferation and differentiation, we used AAV2-mediated gene transfer to produce ectopic expression of IGF-I in the normal adult rat striatum. We then assessed whether the expression of IGF-I would recruit SVZ-derived neuronal precursor cells from the RMS into the striatum. Ectopic expression of IGF-I in the normal adult rat brain significantly increased the number of doublecortin (Dcx)-positive cells and the extent of their migration into the striatum 4 and 8 weeks after AAV2-IGF-I injection but did not promote neuronal differentiation. In vitro migration assays confirmed that IGF-I is an inducer of migration and directs SVZ-derived adult neuronal precursor cell migration by both chemotaxis and chemokinesis. These results demonstrate that overexpression of IGF-I in the normal adult rat brain can override the normal cues directing precursor cell migration along the RMS and can redirect precursor cell migration into a non-neurogenic region. Enhanced expression of IGF-I following brain injury may therefore act as a diffusible factor mediating precursor cell migration to areas of neuronal cell damage.
authors.affiliation: Department of Pharmacology & Clinical Pharmacology, School of Medical Sciences, Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: C
authors.initials: C
authors.lastname: Maucksch
authors.forename: A L
authors.initials: AL
authors.lastname: McGregor
authors.forename: M
authors.initials: M
authors.lastname: Yang
authors.forename: R J
authors.initials: RJ
authors.lastname: Gordon
authors.forename: M
authors.initials: M
authors.lastname: Yang
authors.forename: B
authors.initials: B
authors.lastname: Connor
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D009479:Neuropeptides / Q000096:biosynthesis; D051381:Rats
chemical_list: C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D007334:Insulin-Like Growth Factor I