Lesion‐induced gelsolin upregulation in the hippocampus following entorhinal deafferentation

Abstract

Gelsolin is an actin-binding protein that regulates actin filament-severing and capping activity in the various processes of cell motilities. Here, we report the expression of gelsolin mRNA and protein in the hippocampus following transections of the entorhinal afferents. Northern blot analysis showed that transcript of gelsolin was upregulated in a transient manner in the deafferented hippocampus by 1.3-, 2.1-, 1.7-, and 1.1- folds of controls, respectively, at 1, 3, 7, and 15 days postlesion (dpl). In situ hybridization and immunohistochemistry confirmed the temporal expression of gelsolin specifically in the entorhinally denervated zones: the stratum lacunosum-molecular (SLM) of the hippocampus and the outer molecular layer (OML) of the dentate gyrus (DG), which initiated as early as at 1 dpl, reached the maximum at 3 dpl, remained prominently elevated by 7 dpl, and discernibly higher at 15 dpl than that of controls. Double labeling of either gelsolin mRNA or protein with markers of glial cells (Griffonia simplicifolia IB4 and CD11b for microglial cells, GFAP for astroglial cells) revealed that gelsolin was highly expressed by both activated microglia and astrocytes. The results suggest that the spatiotemporal upregulation of gelsolin in the hippocampus is induced by entorhinal deafferentation, and that gelsolin would participate in the activation processes of both microglial and astroglial cells and thereby, indirectly play important roles in the subsequent lesion-induced neural reorganization in the hippocampus following entorhinal deafferentation.

Gelsolin in Cerebrospinal Fluid as a Potential Biomarker of Epilepsy

“…In addition, through differential proteomic analysis of in vitro blood-brain barrier (BBB) models, gelsolin was reported as a dynamic actor in the cytoskeleton remodeling contributing to BBB leakage [24,44]. Previous studies Fig.…”

“…A third isoform of gelsolin (gelsolin-3) is expressed in cytoplasm of oligodendrocytes in the brain and has been shown to participate in myelin formation and CNS development [28]. The alterations of gelsolin's expression after neural lesion and its role in neural differentiation have been reported in previous studies [24,[29][30][31].…”

“…Gelsolin molecules are localized in the cytoplasm, plasma membrane, intracellular membrane and mitochondrial fraction of a variety of cells [21][22][23][24]. Several previous studies have shown the role of gelsolin in initiating cellular motility in response to various stimuli [20,[24][25][26].…”

High-Throughput LC–MS/MS Proteomic Analysis of a Mouse Model of Mesiotemporal Lobe Epilepsy Predicts Microglial Activation Underlying Disease Development

“…and Gelsolin, mainly expressed by activated microglia and astrocytes 78 and with potential protective role against neuroinflammation in the brain 79 , were also upregulated in KA-injected mice (5.2 fold and 6.4 fold respectively) at 30dpi.…”

Accelerators, Brakes, and Gears of Actin Dynamics in Dendritic Spines

“…An upregulation in gelsolin mRNA [331] and gelsolin protein levels [332] was found in the rat hippocampus following entorhinal deafferentation, suggesting that gelsolin may play a role in brain remodeling following hippocampal injury.…”