Savaskan, N.E. et al. Outgrowth-promoting molecules in the adult hippocampus after perforant path lesion. Eur. J. Neurosci. 12, 1024-1032

Institute of Anatomy, Department of Cell- and Neurobiology, Humboldt University Hospital (Charité), 10098 Berlin, FRG.
European Journal of Neuroscience (Impact Factor: 3.18). 04/2000; 12(3):1024-32. DOI: 10.1046/j.1460-9568.2000.00998.x
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Lesion-induced neuronal plasticity in the adult central nervous system of higher vertebrates appears to be controlled by region- and layer-specific molecules. In this study we demonstrate that membrane-bound hippocampal outgrowth-promoting molecules, as present during the development of the entorhino-hippocampal system and absent or masked in the adult hippocampus, appear 10 days after transection of the perforant pathway. We used an outgrowth preference assay to analyse the outgrowth preference of axons from postnatal entorhinal explants on alternating membrane lanes obtained from hippocampus deafferented from its entorhinal input taken 4, 10, 20, 30 and 80 days post-lesion and from adult control hippocampus. Neurites from the entorhinal cortex preferred to extend axons on hippocampal membranes disconnected from their entorhinal input for 10 days in comparison with membranes obtained from unlesioned adult animals. Membranes obtained from hippocampi disconnected from their entorhinal input for 10 days were equally as attractive for growing entorhinal cortex (EC) axons as membranes from early postnatal hippocampi. Further analysis of membrane properties in an outgrowth length assay showed that entorhinal axons extended significantly longer on stripes of lesioned hippocampal membranes in comparison with unlesioned hippocampal membranes. This effect was most prominent 10 days after lesion, a time point at which axonal sprouting and reactive synaptogenesis are at their peak. Phospholipase treatment of membranes obtained from unlesioned hippocampi of adult animals strongly promoted the outgrowth length of entorhinal axons on these membranes but did not affect their outgrowth preference for deafferented hippocampal membranes. Our results indicate that membrane-bound outgrowth-promoting molecules are reactivated in the adult hippocampus following transection of the perforant pathway, and that neonatal entorhinal axons are able to respond to these molecules. These findings support the hypothesis of a temporal accessibility of membrane-bound factors governing the layer-specific sprouting of remaining axons following perforant path lesion in vivo.

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Available from: Nicolai E. Savaskan, Oct 01, 2015
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    • "Substrates were offered as alternating stripes visualized by addition of fluorescent beads (Molecular Probes). Explant preparation and cultivation were performed as described previously (Savaskan et al., 2000 "
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    • "Although the original structure and function cannot be completely recovered, the sprouting and the synaptogenesis contribute at least in part to the restoration of some inputs to the denervated neurons, processes that are of great importance to the stabilization of nervous network after lesion and generally referred to as structural reorganization [3,5–8]. The molecular mechanisms underlying the reorganization events are still largely unknown, but it has been proved that some growth-associated membrane-bound molecules participate in these processes [9] [10]. Ephrins and their Eph receptors, which are all membrane-bound molecules, seem to be appropriate candidates responsible for the denervationinduced reorganization since their well-known functions in axon guidance and growth in the nervous system of vertebrate and invertebrate [11] [12]. "
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