A neural cell adhesion molecule–derived fibroblast growth factor receptor agonist, the FGL-peptide, promotes early postnatal sensorimotor development and enhances social memory retention

Secher, Thomas; Novitskaia, V.; Berezin, Vladimir; Bock, Elisabeth; Glenthøj, Birte; Klementiev, Boris

doi:10.1016/j.neuroscience.2006.04.059

Cited by 82 publications

(64 citation statements)

References 53 publications

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“…Previously, FGL has been shown to improve learning and memory in a spatial memory task (Cambon et al, 2004). This same loop has also been shown to be neuroprotective in ischemia models and enhance social memory retention (Secher et al, 2006;Skibo et al, 2005). In this study, acute administration of FGL resulted in a significant decrease in immobility in the forced swim test.…”

Section: Discussionsupporting

confidence: 55%

Antidepressant-like effects of intracerebroventricular FGF2 in rats

et al. 2008

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The fibroblast growth factor (FGF) system is altered in post-mortem brains of individuals with major depressive disorder (MDD), but the functional relevance of this observation remains to be elucidated.To this end, we tested whether administering agents that act on FGF receptors would have antidepressant-like effects in rodents. We microinjected either FGF2 (200ng, i.c.v.) or the FG loop (FGL) of neural cell adhesion molecule (NCAM) (5μg, i.c.v.) into the lateral ventricle of rats and tested them on the forced swim test. Activating FGF receptors acutely had an antidepressant-like effect in the forced swim test. Furthermore, chronic FGF2 decreased depression-like behavior as assessed by two independent tests. Finally, the FGF system itself was altered after FGF2 administration. Specifically, there was an increase in FGFR1 mRNA in the dentate gyrus 24 h post FGF2, suggesting the potential for self-amplification of the initial signal. These results support the potential therapeutic use of FGF2 or related molecules in the treatment of MDD and point to alternate mechanisms of neuronal remodeling that may be critical in this treatment.

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Section: Discussionsupporting

confidence: 55%

Antidepressant-like effects of intracerebroventricular FGF2 in rats

et al. 2008

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“…Small synthetic ligands of NCAM derived from the FRM and FGL motifs have recently been shown to mimic many of the cellular functions of NCAM. These peptides stimulate survival of several neuronal types (Neiiendam et al, 2004;Anderson et al, 2005;Skibo et al, 2005), promote memory formation in rodent models (Cambon et al, 2004;Secher et al, 2006), and are neuroprotective against amyloid beta toxicity and ischemic insult both in vitro and in vivo (Skibo et al, 2005;Klementiev et al, 2007Klementiev et al, , 2008.…”

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confidence: 99%

Neural cell adhesion molecule stimulates survival of premyelinating oligodendrocytes via the fibroblast growth factor receptor

Palser

Norman

Saffell

et al. 2009

J of Neuroscience Research

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Axonal signals are critical in promoting the survival and maturation of oligodendrocytes during myelination, with contact-dependent signals thought to play a key role. However, the exact nature of these signals remains unclear. Neural cell adhesion molecule (NCAM) is expressed by both axons and oligodendrocytes and is ideally localized to transduce signals from the axon. This study sought to investigate the influence of NCAM on premyelinating oligodendrocytes in vitro. Both a soluble molecule comprising the extracellular domain of NCAM and a peptide derived from the fibroblast growth factor receptor (FGFR) binding motif within the first fibronectin domain stimulated a dose-dependent increase in survival of premyelinating oligodendrocytes in vitro. The survival effect was blocked by a mitogen-activated protein kinase (MAPK) inhibitor and an FGFR inhibitor, suggesting that activation of MAPK signalling pathways following interaction with the FGFR is involved in the survival effect of NCAM. Furthermore, NCAM presented in a cellular monolayer induced an increase in radial process outgrowth of oligodendrocyte progenitor cells. These data suggest that NCAM may play a role in axon-oligodendrocyte signalling during myelination, leading to an increase in oligodendrocyte survival and process outgrowth following axonal contact.

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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: 77%

“…FGL also enhances presynaptic release in hippocampal cell culture (Cambon et al 2004). 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).…”

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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A neural cell adhesion molecule–derived fibroblast growth factor receptor agonist, the FGL-peptide, promotes early postnatal sensorimotor development and enhances social memory retention

Cited by 82 publications

References 53 publications

Antidepressant-like effects of intracerebroventricular FGF2 in rats

Antidepressant-like effects of intracerebroventricular FGF2 in rats

Neural cell adhesion molecule stimulates survival of premyelinating oligodendrocytes via the fibroblast growth factor receptor

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

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