title: Insulin-like growth factor-1 mRNA is increased in deafferented hippocampus: spatiotemporal correspondence of a trophic event with axon sprouting.
abstract: Deafferentation is known to induce axonal sprouting in adult brain, but the signals that direct this response are not understood. To evaluate the possible roles of insulin-like growth factor-1 (IGF-1) and basic fibroblast growth factor (bFGF) in central axonal sprouting, the present study used in situ hybridization to evaluate IGF-1 and bFGF mRNA expression in entorhinal deafferented rat hippocampus. Alternate tissue sections were processed for Fink-Heimer impregnation of axonal degeneration, Bandeiraea simplicifolia (BS-1) labeling of microglia, and glial fibrillary acidic protein immunocytochemistry. In control hippocampus, IGF-1 mRNA was localized to a few neurons, with no labeled cells in the dentate gyrus molecular layer; bFGF cRNA hybridization was diffuse in dendritic fields but was dense in CA2 stratum pyramidale. Both mRNA species were increased by deafferentation. The distribution of elevated IGF-1 mRNA corresponded precisely to fields of axonal degeneration and was greatest in the dentate gyrus outer molecular layer and stratum lacunosum moleculare. In these fields, IGF-1 mRNA was elevated by 2 days, reached maximal levels at 4 days, and declined by 10 days postlesion. Double labeling revealed that the majority of IGF-1 cRNA-labeled cells were microglia. In deafferented hippocampus, bFGF mRNA was broadly increased across fields both containing and lacking axonal degeneration. In the dentate, bFGF mRNA levels peaked at 5 days postlesion and remained elevated through 14 days. These results demonstrate that reactive microglia within deafferented hippocampal laminae express IGF-1 mRNA just prior to and during the period of reactive axonal growth and suggest that IGF-1 plays a role in directing the sprouting of spared afferents into these fields.
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine 92717.
authors.forename: K M
authors.initials: KM
authors.lastname: Guthrie
authors.forename: T
authors.initials: T
authors.lastname: Nguyen
authors.forename: C M
authors.initials: CM
authors.lastname: Gall
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000648:ultrastructure; D001369:Axons / Q000502:physiology / Q000648:ultrastructure*; D002529:Cerebellar Nuclei / Q000648:ultrastructure; D006624:Hippocampus / Q000502:physiology / Q000648:ultrastructure*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000502:physiology / Q000648:ultrastructure*; D008297:Male; D017628:Microglia / Q000648:ultrastructure*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I