TY - JOUR
T1 - A synthetic NCAM-derived mimetic peptide, FGL, exerts anti-inflammatory properties via IGF-1 and interferon-gamma modulation
AU - Downer, Eric J
AU - Cowley, Thelma R
AU - Cox, Fionnuala
AU - Maher, Francis O
AU - Berezin, Vladimir
AU - Bock, Elisabeth
AU - Lynch, Marina A
N1 - Keywords: Age Factors; Animals; Animals, Newborn; Anti-Inflammatory Agents; Antigens, CD; Antigens, CD40; Cells, Cultured; Cerebral Cortex; Gene Expression Regulation; Hippocampus; Insulin-Like Growth Factor I; Interferon-gamma; Male; Neural Cell Adhesion Molecules; Neuroglia; Neurons; Oncogene Protein v-akt; Rats; Rats, Wistar
PY - 2009
Y1 - 2009
N2 - 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-gamma (IFNgamma), 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 IFNgamma. 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 IFNgamma-induced increases in markers of glial cell activation, including major histocompatibility complex class II (MHCII) and CD40. Finally, the proclivity of FGL to attenuate IFNgamma-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 IFNgamma, 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.
AB - 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-gamma (IFNgamma), 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 IFNgamma. 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 IFNgamma-induced increases in markers of glial cell activation, including major histocompatibility complex class II (MHCII) and CD40. Finally, the proclivity of FGL to attenuate IFNgamma-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 IFNgamma, 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.
U2 - 10.1111/j.1471-4159.2009.06076.x
DO - 10.1111/j.1471-4159.2009.06076.x
M3 - Journal article
C2 - 19457161
SN - 0022-3042
VL - 109
SP - 1516
EP - 1525
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 5
ER -