A neural cell adhesion molecule-derived peptide, FGL, attenuates glial cell activation in the aged hippocampus

作者：Ojo Bunmi; Rezaie Payam; Gabbott Paul L; Cowely Thelma R; Medvedev Nikolay I; Lynch Marina A; Stewart Michael G^*

来源：Experimental Neurology, 2011, 232(2): 318-328.

DOI：10.1016/j.expneurol.2011.09.025

• Ageing
• Microglia
• Astrocytes
• Hippocampus
• NCAM-derived peptide

Neuroglial activation is a typical hallmark of ageing within the hippocampus, and correlates with age-related cognitive deficits. We have used quantitative immunohistochemistry and morphometric analyses to investigate whether systemic treatment with the Neural Cell Adhesion Molecule (NCAM)-derived peptide FG Loop (FGL) specifically alters neuroglial activation and population densities within the aged rat hippocampus (22 months of age). A series of 50 mu m paraformaldehyde/acrolein-fixed sections taken throughout the dorsal hippocampus (5 animals per group) were immunostained to detect astrocytes (GFAP and S100 beta) and microglial cells (CD11b/OX42 and MHCII/OX6), and analysed using computerised image analysis and optical segmentation (Image-Pro Plus, Media Cybernetics). FGL treatment reduced the density of CD11b+ and MHCII+ microglia in aged animals, concomitant with a reduction in immunoreactivity for these phenotypic markers. FGL treatment also markedly reduced GFAP immunoreactivity within all hippocampal sub-fields in aged animals, without exerting an appreciable effect on the density of S100 beta+ cells. These results demonstrate that FGL can indeed regulate neuroglial activation and reduce microglial cell density in the aged hippocampus, and support its potential use as a therapeutic agent in age-related brain disorders.

• 出版日期2011-12