Effects of acidic fibroblast growth factor on higpocampal long‐term potentiation in fasted rats

Hisajima, Hiroshi; Saito, Hiroshi; Abe, Kazuho; Nishiyama, Nobuyoshi

doi:10.1002/jnr.490310319

Cited by 32 publications

(8 citation statements)

References 27 publications

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“…However, after administration of HFS, FGL was found to facilitate both PTP and LTP up to 3 h post-HFS in the anesthetized rat and up to 24 h post-HFS in the awake rat. Although FGL is likely to stimulate the FGFR differently than the FGFs molecules (Hinsby et al 2004a,b;Kiselyov et al 2005) and may act also on other receptors, this result corroborates the investigation of Zhao and colleagues reporting a severe impairment of in vitro MPP-LTP in the Fgfr1 conditional knock-out mouse (Zhao et al 2007) and an earlier study showing that icv injection of human acidic FGF facilitates the generation of LTP by a weak tetanus in the awake rat (Hisajima et al 1992). Interestingly however, a recent study reports that FGL alleviated the deficiency in LTP displayed by aged rats, but had no effect on LTP 1 h post-induction in young Wistar rats in vivo (Downer et al 2010).…”

Section: Discussionsupporting

confidence: 85%

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

Dallérac¹,

Zerwas²,

Novikova³

et al. 2011

Learn. Mem.

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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: Discussionsupporting

confidence: 85%

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

Dallérac¹,

Zerwas²,

Novikova³

et al. 2011

Learn. Mem.

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“…injections of FGF-1. LTP can be induced using a subthreshold stimulation in combination with administration of FGF-1; however, LTP cannot be induced using the subthreshold stimulation alone (Hisajima et al 1992). Further evidence came from a study using an FGF-1 fragment analog (amino acid residues 1 through 29 of FGF-1 with an alanine substituted at position 16) on accelerated senescence-prone mice.…”

Section: Learning and Memorymentioning

confidence: 98%

“…A similar model system demonstrating growth factor effects on LTP is provided by the following example: Transection of the fimbria-fornix pathway decreases the frequency of LTP generation. Intracerebroventricular injection of epidermal growth factor (EGF) or FGF-2 facilitated LTP generation in the fimbria-fornix lesioned rats, suggesting that EGF and FGF-2 can improve hippocampal LTP impairment after loss of subcortical afferents (Abe et al 1992). …”

Section: Learning and Memorymentioning

confidence: 99%

Fibroblast growth factors and their receptors in the central nervous system

2003

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Fibroblast growth factors (FGFs) and their receptors constitute an elaborate signaling system that participates in many developmental and repair processes of virtually all mammalian tissues. Among the 23 FGF members, ten have been identified in the brain. Four FGF receptors (FGFRs), receptor tyrosine kinases, are known so far. Ligand binding of these receptors greatly depends on the presence of heparan sulfate proteoglycans, which act as low affinity FGFRs. Ligand binding specificity of FGFRs depends on the third extracellular Ig-like domain, which is subject to alternative splicing. Activation of FGFRs triggers several intracellular signaling cascades. These include phosphorylation of src and PLCgamma leading finally to activation of PKC, as well as activation of Crk and Shc. SNT/FRS2 serves as an alternative link of FGFRs to the activation of PKC and, in addition, activates the Ras signaling cascade. In the CNS, FGFs are widely expressed; FGF-2 is predominantly synthesized by astrocytes, whereas other FGF family members, e.g., FGF-5, FGF-8, and FGF-9, are primarily synthesized by neurons. During CNS development FGFs play important roles in neurogenesis, axon growth, and differentiation. In addition, FGFs are major determinants of neuronal survival both during development and during adulthood. Adult neurogenesis depends greatly on FGF-2. Finally, FGF-1 and FGF-2 seem to be involved in the regulation of synaptic plasticity and processes attributed to learning and memory.

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“…, 2004; Sanchez‐Heras et al. , 2006) and a number of studies have shown that FGFR and NCAM are involved in learning and memory consolidation (Hisajima et al. , 1992; Cremer et al.…”

Section: Introductionmentioning

confidence: 99%

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

Popov

Medvedev

Kraev

et al. 2008

Eur J of Neuroscience

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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.

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Effects of acidic fibroblast growth factor on higpocampal long‐term potentiation in fasted rats

Cited by 32 publications

References 27 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

Fibroblast growth factors and their receptors in the central nervous system

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

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