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

Abstract

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.

Deep-brain magnetic stimulation promotes adult hippocampal neurogenesis and alleviates stress-related behaviors in mouse models for neuropsychiatric disorders

“…The DMS protocol we applied exerts high frequency oscillated stimulation in the brain of animal models and rescues the deficient LTP impaired by restraint stress in rats. On the other hand, LTP induction in the anesthetized rats increases neurogenesis in the dentate gyrus and FGFR activation by the neural cell adhesion molecule promotes neural progenitor proliferation by enhancing LTP [42,43]. Therefore, the study suggests that DMS administration may promote adult neurogenesis by inducing high frequency theta-burst stimulation and LTP in the hippocampus.…”

Fibroblast Growth Factor-2 Signaling in Neurogenesis and Neurodegeneration

“…Rats showed memory improvement in water maze testing and fear conditioning paradigms immediately following ICV FGL administration, and in primary cultured rat hippocampal neurons, FGL promoted synapse formation and enhanced presynaptic function via FGFR1 activation [67]. Dallérac et al (2011) then demonstrated facilitation of LTP induction and maintenance in awake, behaving rats for up to 24 hours following ICV infusion of FGL, as well as altered neurogenesis associated with LTP [68]. …”

The Neural Cell Adhesion Molecule-Derived (NCAM)-Peptide FG Loop (FGL) Mobilizes Endogenous Neural Stem Cells and Promotes Endogenous Regenerative Capacity after Stroke

“…Moreover, positive effects on neurogenesis in the dentate gyrus as well as neuroprotection in vitro have been described (Neiiendam et al 2004;Dallerac et al 2011). Our own previous data suggest a mobilization of endogenous NSC via systemic FGL-treatment under physiologic conditions in vivo .…”

“…Contrary to NCAM and due to its small size of only 15 amino acids, FGL readily crosses the blood-brain-barrier after systemic administration (Secher et al 2006;Klementiev et al 2007;Chen et al 2010). FGL has been shown to enhance spatial learning and memory, probably by facilitating plasticity in the hippocampus, and it exerts anti-inflammatory effects upon glia cells (Dallerac et al 2011, Knafo et al, 2012, Cox et al, 2013. We recently showed that FGL both mobilizes endogenous neural stem cells (NSC) and enhances the generation of oligodendrocytes in vitro .…”