A synthetic NCAM―derived mimetic peptide, FGL, exerts anti― inflammatory properties via IGF―1 and interferon―γ modulation

Microglial cell activity increases in the rat hippocampus during normal brain aging. The neural cell adhesion molecule (NCAM)-derived mimetic peptide, FG loop (FGL), acts as an anti-inflammatory agent in the hippocampus of the aged rat, promoting CD200 ligand expression while attenuating glial cell activation and subsequent pro-inflammatory cytokine production. The aim of the current study was to determine if FGL corrects the age-related imbalance in hippocampal levels of insulin-like growth factor-1 (IGF-1) and pro-inflammatory interferon-γ (IFNγ), and subsequently attenuates the glial reactivity associated with aging. Administration of FGL reversed the age-related decline in IGF-1 in hippocampus, while abrogating the age-related increase in IFNγ. FGL robustly promotes IGF-1 release from primary neurons and IGF-1 is pivotal in FGL induction of neuronal Akt phosphorylation and subsequent CD200 ligand expression in vitro. In addition, FGL abrogates both age- and IFNγ-induced increases in markers of glial cell activation, including major histocompatibility complex class II (MHCII) and CD40. Finally, the proclivity of FGL to attenuate IFNγ-induced glial cell activation in vitro is IGF-1-dependent. Overall, these findings suggest that FGL, by correcting the age-related imbalance in hippocampal levels of IGF-1 and IFNγ, attenuates glial cell activation associated with aging. These findings also highlight a novel mechanism by which FGL can impact on neuronal CD200 ligand expression and subsequently on glial cell activation status.