Journal
HIPPOCAMPUS
Volume 21, Issue 1, Pages 81-92Publisher
WILEY
DOI: 10.1002/hipo.20725
Keywords
entorhinal lesion; synaptic plasticity; proteoglycan; dentate gyrus; gene expression
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Funding
- NIH, State of Virginia [NS-044372, NS-057758, NS-056247, CNI 07-302F]
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS056247, R01NS057758, R01NS044372, R56NS044372] Funding Source: NIH RePORTER
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This study documents the spatial and temporal expression of three structurally related chondroitin sulfated proteoglycans (CSPGs) during synaptic regeneration induced by brain injury. Using the unilateral entorhinal cortex (EC) lesion model of adaptive synaptogenesis, we documented mRNA and protein profiles of phosphacan and its two splice variants, full length receptor protein tyrosine phosphatase (RPTP beta) and the short transmembrane receptor form (sRPTP beta), at 2, 7, and 15 days postlesion. We report that whole hippocampal sRPTP beta protein and mRNA are persistently elevated over the first two weeks after UEC. As predicted, this transmembrane family member was localized adjacent to synaptic sites in the deafferented neuropil and showed increased distribution over that zone following lesion. By contrast, whole hippocampal phosphacan protein was not elevated with deafferentation; however, its mRNA was increased during the period of sprouting and synapse formation (7d). When the zone of synaptic reorganization was sampled using molecular layer/granule cell (ML/GCL) enriched dissections, we observed an increase in phosphacan protein at 7d, concurrent with the observed hippocampal mRNA elevation. Immunohistochemistry also showed a shift in phosphacan distribution from granule cell bodies to the deafferented ML at 2 and 7d postlesion. Phosphacan and sRPTP beta were not colocalized with glial fibrillary acid protein (GFAP), suggesting that reactive astrocytes were not a major source of either proteoglycan. While transcript for the developmentally prominent full length RPTP beta was also increased at 2 and 15d, its protein was not detected in our adult samples. These results indicate that phosphacan and RPTP beta splice variants participate in both the acute degenerative and long-term regenerative phases of reactive synaptogenesis. These results suggest that increase in the transmembrane sRPTP beta tyrosine phosphatase activity is critical to this plasticity, and that local elevation of extracellular phosphacan influences dendritic organization during synaptogenesis. (C) 2009 Wiley-Liss, Inc.
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