A cell adhesion molecule mimetic, FGL peptide, induces alterations in synapse and dendritic spine structure in the dentate gyrus of aged rats: a three‐dimensional ultrastructural study

Abstract

The FGL peptide is a neural cell adhesion molecule (NCAM) mimetic comprising a 15-amino-acid-long sequence of the FG loop region of the second fibronectin type III module of NCAM. It corresponds to the binding site of NCAM for the fibroblast growth factor receptor 1. FGL improves cognitive function through enhancement of synaptic function. We examined the effect of FGL on synaptic and dendritic structure in the brains of aged (22-month-old) rats that were injected subcutaneously (8 mg/kg) at 2-day intervals until 19 days after the start of the experiment. Animals were perfused with fixative, brains removed and coronal sections cut at 50 microm. The hippocampal volume was measured, tissue embedded and ultrathin sections viewed in a JEOL 1010 electron microscope. Analyses were made of synaptic and dendritic parameters following three-dimensional reconstruction via images from a series of approximately 100 serial ultrathin sections. FGL affected neither hippocampal volume nor spine or synaptic density in the middle molecular layer of the dentate gyrus. However, it increased the ratio of mushroom to thin spines, number of multivesicular bodies and also increased the frequency of appearance of coated pits. Three-dimensional analysis showed a significant decrease in both post-synaptic density and apposition zone curvature of mushroom spines following FGL treatment, whereas for thin spines the convexity of the apposition zone increased. These data indicate that FGL induces large changes in the fine structure of synapses and dendritic spines in hippocampus of aged rats, complementing data showing its effect on cognitive processes.

Partial kindling induces neurogenesis, activates astrocytes and alters synaptic morphology in the dentate gyrus of freely moving adult rats

“…(Popov et al, 2004(Popov et al, , 2008Popov and Stewart, 2009). However, a more detailed examination of the tissue showed prominent ultrastructural changes after kindling in the right hippocampus.…”

Influence of matrix metalloproteinase MMP-9 on dendritic spine morphology

“…No changes were found in the size of mushroom and thin spines and their PSDs in MPP-9 TR compared with WT rats. To describe possible changes in spine shape in the active zone area, we analysed the curvature of the PSD area of mushroom and thin spines [as described in the Materials and Methods and in Popov et al (Popov et al, 2008)] but no significant changes were found in spine curvature. The curvature of mushroom spines in the PSD area was 8 50.6148;P50.4768); the curvature of thin spines in the PSD area was, respectively, -6.25¡0.53˚for WT and -1.34¡0.62˚for MMP-9 TR rats (F 1,8 51.1313; P50.3474).…”

“…Shaft synapses are a fourth category where the synapse contacts directly the dendritic shaft. There were three animals in each group for the three-dimensional analyses, which were made from the stratum radiatum of CA1; 25 thin and 25 mushroom spines were reconstructed to analyse spine volume, surface area and curvature of the PSD, as described previously (Popov et al, 2008). The volume and surface area of PSDs on these reconstructed spines were also analysed.…”

“…All data were averaged to receive 1 mean per animal for each parameter and all statistics for three-dimensional analyses were calculated using this data (one value per animal). The curvature of dendritic spines was measures as described previously (Popov et al, 2008). All data from digital reconstructive analysis was evaluated to give 1 value for each individual animal in each data set.…”

The neural cell adhesion molecule-derived peptide FGL facilitates long-term plasticity in the dentate gyrus in vivo

“…FGL has indeed been shown to influence connectivity in the DG (Popov et al 2008;Stewart et al 2010), as well as in hippocampal-dependent memories (Cambon et al 2004;Secher et al 2009); further, FGFR1 have been shown to influence plasticity in the DG (Zhao et al 2007). The cellular mechanisms associated with long-term potentiation (LTP) in the first hours following its induction are thought to primarily involve posttranslational modifications (Bliss and Collingridge 1993).…”