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- Title
Regulation of Axonal Elongation and Pathfinding from the Entorhinal Cortex to the Dentate Gyrus in the Hippocampus by the Chemokine Stromal Cell-Derived Factor 1α.
- Authors
Ohshima, Yoichi; Kubo, Takekazu; Koyama, Ryuta; Ueno, Masaki; Nakagawa, Masanori; Yamashita, Toshihide
- Abstract
During the early developmental stage, a neural circuit is established between the entorhinal cortex (EC) and the hippocampal dentate gyrus (DG) via the perforant pathway. However, the manner in which the perforant fibers are navigated has mostly remained a mystery. Here, we analyzed the functional role of a chemokine, namely, stromal cell-derived factor 1α (SDF-1α), in the navigation of the perforant fibers. SDF-1α was observed to promote neurite growth, which is dependent on mDia1, in cultured entorhinal cortical neurons obtained from rats at postnatal day 0. We then used entorhino-hippocampal cocultures comprising green fluorescence-labeled EC and DG slices to assess the projection of the perforant fibers from the EC. Although the specific laminar termination of the entorhinal axons was observed with this system, the number of appropriately terminating entorhinal axons decreased significantly when the SDF-1α signaling pathway was blocked by a neutralizing antibody against SDF-1α or by the specific SDF-1α receptor antagonist AMD3100 (1,1α-[1,4-phenylenebis(methylene)]bis-1,4,8,11-tetra-azacyclotetradecane octahydrochloride). Furthermore, inhibition of the SDF-1α signaling pathway resulted in a decrease in the immunoreactivity for PSD-95 (postsynaptic density protein-95) in the DG, possibly because of a reduction in the number of projecting perforant fibers. These results demonstrate that SDF-1α plays a critical role in promoting the growth of perforant fibers from the EC to the DG.
- Subjects
DENTATE gyrus; HIPPOCAMPUS (Brain); CHEMOKINES; NEURONS; AXONS
- Publication
Journal of Neuroscience, 2008, Vol 28, Issue 33, p8344
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.1670-08.2008