engleski

Dendritic reorganization of granule cells in the fascia dentata of the Thy1-GFP mouse following entorhinal cortex lesion

Neurons denervated after brain injury remodel their dendritic tree. Although this phenomenon has been described many years ago, neither the precise dynamics of the structural changes nor the underlying molecular mechanisms have yet been unraveled. The entorhinal cortex lesion (ECL) model is one of the classical models for the analysis of denervation-induced neuronal changes in the CNS. However, most of the data stem from ECL in rats and data on the reorganization of neurons in the denervated mouse fascia dentata are scarce. Since this limits the use of genetic tools, we have analyzed the dendritic reorganization of denervated granule cells in mice. Thy1-GFP mice bred on a C57BL/6 background were used in these studies. Entorhino-hippocampal fibers were transected using a wire knife and animals survived 3, 7, 10, 30, 90 and 180 days post lesion (dpl). Denervated GFP-labeled granule cells located in the dorsal fascia dentata were 3D-reconstructed in their entirety using confocal microscopy and Neurolucida. This morphometric analysis revealed that ECL results in a profound atrophy of denervated mouse granule cells. Dendritic length and the number of dendritic segments progressively decreased and reached a minimum around 90dpl. Dendrites located within the denervated portion of the molecular layer were predominately affected. By 180dpl a partial recovery of dendritic length but not of dendritic segments was observed. Spine density showed a similar decrease with a minimum around 90dpl (70% of all spines lost ; spine density decreased to 50% of control values). By 180dpl a partial recovery in spine number and density was seen. Using intracellular fillings of neurons in fixed slices we found no significant morphological differences between GFP-positive and GFP-negative granule cells upon denervation. Taken together, this study provides normative data on the ECL model in mice and reveals that granule cell atrophy in mice following denervation is more severe than in rats.

mouse dentate gyrus; green fluorescent protein; morphometry; confocal microscopy; regeneration

nije evidentirano