Article type: Research Article
Authors: Feeney, Erin J. | Stephenson, Diane | Kleiman, Robin | Bove, Susan | Cron, Courtney; | Moody, Lara; | Robinson, Mercedes; | Ramirez, Julio J.;
Affiliations: Neuroscience Program, Davidson College, Davidson, NC, USA | Department of Psychology, Davidson College, Davidson, NC, USA | Pfizer Neuroscience Research Unit, Pfizer Global Research and Development, Pfizer Inc., Groton, CT, USA
Note: [] Present address: Diane Stephenson at Critical Path Institute, Tucson, AZ. E-mail: dstephenson@c-path.org
Note: [] Present address: Robin Kleiman at Selventa, Cambridge, MA. E-mail: rkleiman@selventa.com
Note: [] Corresponding author: Julio J. Ramirez, Ph.D., Department of Psychology and Neuroscience Program, Box 7017, Watson Building, Room 202, Davidson College, Davidson, North Carolina 28035, USA. Tel.: +1 704 894 2888; Fax: +1 704 894 2512; E-mail: juramirez@davidson.edu
Abstract: Purpose: Transgenic manipulation of mouse physiology facilitates the preclinical study of genetic risk factors, neural plasticity, and reactive processes accompanying Alzheimer's disease. Alternatively, entorhinal cortex lesions (ECLs) model pathophysiological denervation and axonal sprouting in rat. Given reports of anatomical differences between the mouse and rat hippocampus, application of the ECL paradigm to transgenic mice first requires comprehensive characterization of axonal sprouting in the wild-type. Methods: Adult male C57BL/6 mice sustained unilateral transections of the perforant pathway. Subjects were sacrificed at 1, 4, 10, 18, and 28 days postlesion, and hippocampal sections were stained for AChE, the postsynaptic terminal marker drebrin, and the presynaptic terminal proteins SNAP-25, GAP-43, synapsin, and synaptophysin. To examine synaptic turnover and reinnervation, ipsilateral-to-contralateral staining densities were determined within the dentate molecular layer, and shrinkage-corrected ratios were compared to 28 day-yoked sham cases. Results: At 28 days postlesion, ipsilateral terminal marker densities exhibited significant depression. In contrast, qualitative analyses at earlier time points suggested altered AChE staining patterns and increased SNAP-25 and synapsin immunoreactivity in the inner molecular layer (IML) of the dentate gyrus. Conclusions: C57BL/6 mice exhibit synaptic reorganization following perforant path transections. The IML may provide a key target for evaluation and intervention in ECL mouse models.
Keywords: Reactive sprouting, C57BL/6, AChE, drebrin, GAP-43, SNAP-25, synapsin, synaptophysin, entorhinal cortex, hippocampus
DOI: 10.3233/RNN-130311
Journal: Restorative Neurology and Neuroscience, vol. 31, no. 5, pp. 517-531, 2013
