Entorhinal deafferentation induces upregulation of SPARC in the mouse hippocampus.

SPARC is a matricellular protein that modulates cell-cell and cell-matrix interactions by virtue of its antiproliferative and counteradhesive properties. Here, we report the denervation-induced upregulation of SPARC mRNA and protein in the mouse hippocampus following transections of the entorhinal afferents. Northern blot analysis showed that SPARC mRNA was upregulated in a transient manner in the deafferented mouse hippocampus. In situ hybridization and immunohistochemistry confirmed the temporal upregulation of both SPARC mRNA and protein specifically in the denervated areas, which initiated at 7 days postlesion, reached the maximum at 15 as well as 30 days postlesion, and subsided towards normal levels by 60 days postlesion. Double labeling by either a combination of in situ hybridization for SPARC mRNA with immunohistochemistry for glial fibrillary acidic protein or double immunofluorescence staining for both proteins in the hippocampus revealed that SPARC-expressing cells are reactive astrocytes. In respect to the spatiotemporal alterations of SPARC expression in the denervated hippocampus, we suggest that SPARC may be involved in modulation of the denervation-induced plasticity processes such as glial cell proliferation, axonal sprouting and subsequent synaptogenesis in the hippocampus following entorhinal deafferentation.