A synthetic NCAM‐derived peptide, FGL, protects hippocampal neurons from ischemic insult both <i>in vitro</i> and <i>in vivo</i>

Skibo, G. G.; Lushnikova, Iryna; Воронин, К. В.; Дмитриева, О. С.; Novikova, Tatiana; Klementiev, Boris; Vaudano, Elisabetta; Berezin, Vladimir; Bock, Elisabeth

doi:10.1111/j.1460-9568.2005.04345.x

Cited by 59 publications

(55 citation statements)

References 43 publications

(51 reference statements)

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“…This might be interpreted as a loss of input specificity, one of the basic properties of LTP that made it originally suitable as a model for memory mechanisms, which would then imply that FGL may not engender only beneficial effects. Another possibility, more in line with the positive effects of FGL on memory (Cambon et al 2004;Skibo et al 2005;Secher et al 2006Secher et al , 2009Klementiev et al 2007), is that the apparent "heterosynaptic" LTP reflects, in fact, a facilitation of processes homosynaptic in nature, in the same way as it has been suggested for the requirement of homosynatic activity in heterosynaptic LTD (Abraham et al 2007). Indeed, stimulation of the FGFR-1 with FGF, NCAM or L1 has been shown to induce a rise in intracellular calcium concentration ([Ca 2+ ]i) mediated by the activation of L-and T-type voltagedependent calcium channels (VDCC) in neural as well as non-neural cell cultures (Archer et al 1999;Rosenthal et al 2005;Kiryushko et al 2006).…”

Section: Discussionmentioning

confidence: 73%

“…In vivo, chronic administration of the peptide improves associative, spatial as well as social memory, and reduces phencyclidine-induced impairment in spatial learning (Cambon et al 2004;Secher et al 2006Secher et al , 2009. Remarkably, a single acute administration of FGL appears sufficient to alleviate Ab, or ischemia-induced neuropathology and cognitive impairment (Skibo et al 2005;Klementiev et al 2007;Secher et al 2009). Further, a recent study by Stewart and colleagues demonstrated that FGL treatment alters spine morphology and synapse distribution (Stewart et al 2010).…”

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

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

Dallérac¹,

Zerwas²,

Novikova³

et al. 2011

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The neural cell adhesion molecule (NCAM) is known to play a role in developmental and structural processes but also in synaptic plasticity and memory of the adult animal. Recently, FGL, a NCAM mimetic peptide that binds to the Fibroblast Growth Factor Receptor 1 (FGFR-1), has been shown to have a beneficial impact on normal memory functioning, as well as to rescue some pathological cognitive impairments. Whether its facilitating impact may be mediated through promoting neuronal plasticity is not known. The present study was therefore designed to test whether FGL modulates the induction and maintenance of synaptic plasticity in the dentate gyrus (DG) in vivo. For this, we first assessed the effect of the FGL peptide on synaptic functions at perforant path-dentate gyrus synapses in the anesthetized rat. FGL, or its control inactive peptide, was injected locally 60 min before applying high-frequency stimulation (HFS) to the medial perforant path. The results suggest that although FGL did not alter basal synaptic transmission, it facilitated both the induction and maintenance of LTP. Interestingly, FGL also modified the heterosynaptic plasticity observed at the neighboring lateral perforant path synapses. The second series of experiments, using FGL intracerebroventricular infusion in the awake animal, confirmed its facilitating effect on LTP for up to 24 h. Our data also suggest that FGL could alter neurogenesis associated with LTP. In sum, these results show for the first time that enhancing NCAM functions by mimicking its heterophilic interaction with FGFR facilitates hippocampal synaptic plasticity in the awake, freely moving animal.

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Section: Discussionmentioning

confidence: 73%

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

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

Dallérac¹,

Zerwas²,

Novikova³

et al. 2011

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“…16 FGL proved to exert beneficial effects in different models of neurological or psychiatric diseases. 6,7,[11][12][13][14]20 In the present study, repeated administration of the peptide mimetic FGL affected kindling progression as well as associated alterations in the number of neuronal progenitor cells and early postmitotic cells. The impact of FGL on kindling progression is indicated by a reduced number of stimulations necessary to induce a generalized seizure.…”

Section: ■ Results and Discussionmentioning

confidence: 88%

“…5 Neuroprotective effects have been observed in vitro using a model of oxygen−glucose deprivation as well as in vivo in a gerbil transient global ischemia model. 7 Moreover, FGL affected long-term plasticity, synapse and dendritic spine structure, and synaptogenesis. 8−10 Beneficial effects were also reported from a mouse aging model, a chronic stress model, and an Alzheimer's model indicating neuroprotective and cognition-enhancing properties.…”

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confidence: 99%

Impact of the Neural Cell Adhesion Molecule-Derived Peptide FGL on Seizure Progression and Cellular Alterations in the Mouse Kindling Model

Zellinger

Salvamoser

Seeger

et al. 2014

ACS Chem. Neurosci.

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The neural cell adhesion molecule peptide mimetic fibroblast growth loop (FGL) proved to exert neuroprotective, neurotrophic, and anti-inflammatory effects in different in vitro and in vivo experiments. Based on this beneficial efficacy profile, it is currently in clinical development for neurodegenerative diseases and brain insults. Here, we addressed the hypothesis that the peptide might affect development of seizures in a kindling paradigm, as well as associated behavioral and cellular alterations. Both doses tested, 2 and 10 mg/kg FGL, significantly reduced the number of stimulations necessary to induce a generalized seizure. FGL did not exert relevant effects on the behavioral patterns of kindled animals. As expected, kindling increased the hippocampal cell proliferation rate. Whereas the low dose of FGL did not affect this kindling-associated alteration, 10 mg/kg FGL proved to attenuate the expansion of the doublecortin-positive cell population. These data suggest that FGL administration might have an impact on disease-associated alterations in the hippocampal neuronal progenitor cell population. In conclusion, the effects of the peptide mimetic FGL in the kindling model do not confirm a disease-modifying effect with a beneficial impact on the development or course of epilepsy. The results obtained with FGL rather raise some concern regarding a putative effect, which might promote the formation of a hyperexcitable network. Future studies are required to further assess the risks in models with development of spontaneous seizures.

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“…It enhances hippocampal function (Cambon et al, 2004, Dallerac et al, 2011 and plays a role in neuronal development (Cambon et al, 2004, Li et al, 2009, Dallerac et al, 2011. FGL has also been shown to be protective against 6-hydroxydopamine and amyloid-β (Aβ) in vitro (Neiiendam et al, 2004) and decreases neuronal damage in hippocampal organotypic slice cultures subjected to oxygen-glucose (Skibo et al, 2005). Protective effects of FGL in vivo have also been reported; thus it has been shown to attenuate the increased Aβ-immunoreactivity and deficit in cognitive function induced by intracerebroventricular administration of pre-aggregated Aβ [25][26][27][28][29][30][31][32][33][34][35] (Klementiev et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

The neural cell adhesion molecule-derived peptide, FGL, attenuates lipopolysaccharide-induced changes in glia in a CD200-dependent manner

et al. 2013

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Please cite this article as: F. Fionnuala Cox, V. Berezin, E. Bock, M.A. Lynch, The neural cell adhesion moleculederived peptide, FGL, attenuates lipopolysaccharide-induced changes in glia in a CD200-dependent manner, Neuroscience (2013), doi: http://dx.doi.org/10.1016/j.neuroscience. 2012.12.030 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 ABSTRACT Fibroblast growth loop (FGL) is a neural cell adhesion molecule (NCAM)-mimetic peptide that mimics the interaction of NCAM with fibroblast growth factor receptor (FGFR). FGLincreases neurite outgrowth and promotes neuronal survival in vitro, and it has also been shown to have neuroprotective effects in vivo. More recent evidence has indicated that FGL has anti-inflammatory effects, decreasing age-related changes in microglial activation and production of inflammatory cytokines. These changes have been associated with an FGLinduced increase in expression of the glycoprotein, CD200, which interacts with its receptor to help maintain microglia in a quiescent state. However whether the FGL-induced antiinflammatory effects are CD200-dependent has not been examined. The objective of this study was to address this question. Mixed glia were prepared from brain tissue of neonatal wildtype and CD200-deficient mice and preincubated with FGL prior to stimulation with lipopolysaccharide (LPS). Cells were assessed for mRNA expression of markers of microglial activation, CD11b, CD40 and intercellular adhesion molecule 1 (ICAM) and also the inflammatory cytokines, interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α, while supernatant concentrations of these cytokine were also assessed. LPS significantly increased all these parameters and the effect was greater in cells prepared from CD200-deficient mice. Whereas FGL attenuated the LPS-induced changes in cells from wildtype mice, it did not do so in cells from CD200-deficient mice. We conclude that the FGL-induced changes in microglial activation are CD200-dependent and demonstrate that the interaction of astrocytes with microglia is critically important for modulating microglial activation.

show abstract

A synthetic NCAM‐derived peptide, FGL, protects hippocampal neurons from ischemic insult both in vitro and in vivo

Cited by 59 publications

References 43 publications

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

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

Impact of the Neural Cell Adhesion Molecule-Derived Peptide FGL on Seizure Progression and Cellular Alterations in the Mouse Kindling Model

The neural cell adhesion molecule-derived peptide, FGL, attenuates lipopolysaccharide-induced changes in glia in a CD200-dependent manner

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