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.

Stimulation of Adult Oligodendrogenesis by Myelin-Specific T Cells

“…This corresponds well to in situ hybridization results that demonstrated elevated IGF-1 mRNA expression in the deafferented outer molecular layer up to 12 days post lesion in rats. 46,103 IGF-1 is expressed in glial cells and neurons in normal CNS. 104,105 As mentioned for BDNF, the inability to detect a T cell-mediated effect on IGF-1 mRNA expression at 2 and 7 days post lesion in T PLP mice could also be due to dilution bias.…”

“…45,46 At 2 days post lesion, IGF-1 mRNA expression remained at baseline levels in T PLP , T OVA , and naïve mice ( Figure 6B; see also Supplemental Table S1 at http://ajp.amjpathol.org). In contrast, at 7 days post lesion, when T OVA and naïve mice demonstrated a close to twofold increase in IGF-1 mRNA expression (P Ͻ 0.01 and P Ͻ 0.01, respectively; see also Supplemental Table S1 at http://ajp.amjpathol.org), T PLP mice failed to demonstrate a lesion-induced increase in IGF-1 mRNA expression ( Figure 6B; see also Supplemental Table S1 at http://ajp.amjpathol.org).…”

Post-transcriptional regulation of zenk expression associated with zebra finch vocal development

“…The second series was collected and processed for zenk immunocytochemistry as described above for Experiment 1. The third series was collected into 20 ml scintillation vials containing icecold 2× SSC for fixed-tissue in situ hybridization [9].…”

Adeno-Associated Virus Vector Expressing Nerve Growth Factor Enhances Cholinergic Axonal Sprouting after Cortical Injury in Rats

“…Indeed, within the partially denervated hippocampus, gene expression and/or immunocytochemical labeling for several neurotrophic factors increases during the first week after lesion; these factors include basic fibroblast growth factor (Gomez-Pinilla et al, 1992;Fagan et al, 1997), ciliary neurotrophic factor (Guthrie et al, 1997), insulin growth factor-1 (Guthrie et al, 1995), and NGF (Conner et al, 1994). Of these factors, NGF may be especially important in regulating lesioninduced septodentate sprouting.…”