title: Age-related changes in the hippocampus (loss of synaptophysin and glial-synaptic interaction) are modified by systemic treatment with an NCAM-derived peptide, FGL.
abstract: Altered synaptic morphology, progressive loss of synapses and glial (astrocyte and microglial) cell activation are considered as characteristic hallmarks of aging. Recent evidence suggests that there is a concomitant age-related decrease in expression of the presynaptic protein, synaptophysin, and the neuronal glycoprotein CD200, which, by interacting with its receptor, plays a role in maintaining microglia in a quiescent state. These age-related changes may be indicative of reduced neuroglial support of synapses. FG Loop (FGL) peptide synthesized from the second fibronectin type III module of neural cell adhesion molecule (NCAM), has previously been shown to attenuate age-related glial cell activation, and to 'restore' cognitive function in aged rats. The mechanisms by which FGL exerts these neuroprotective effects remain unclear, but could involve regulation of CD200, modifying glial-synaptic interactions (affecting neuroglial 'support' at synapses), or impacting directly on synaptic function. Light and electron microscopic (EM) analyses were undertaken to investigate whether systemic treatment with FGL (i) alters CD200, synaptophysin (presynaptic) and PSD-95 (postsynaptic) immunohistochemical expression levels, (ii) affects synaptic number, or (iii) exerts any effects on glial-synaptic interactions within young (4 month-old) and aged (22 month-old) rat hippocampus. Treatment with FGL attenuated the age-related loss of synaptophysin immunoreactivity (-ir) within CA3 and hilus (with no major effect on PSD-95-ir), and of CD200-ir specifically in the CA3 region. Ultrastructural morphometric analyses showed that FGL treatment (i) prevented age-related loss in astrocyte-synaptic contacts, (ii) reduced microglia-synaptic contacts in the CA3 stratum radiatum, but (iii) had no effect on the mean number of synapses in this region. These data suggest that FGL mediates its neuroprotective effects by regulating glial-synaptic interaction.
authors: Department of Life Sciences, The Open University, Walton Hall, Milton Keynes MK7 6AA, UK.
authors: Bunmi
authors: B
authors: Ojo
authors: Payam
authors: P
authors: Rezaie
authors: Paul L
authors: PL
authors: Gabbott
authors: Heather
authors: H
authors: Davies
authors: Frances
authors: F
authors: Colyer
authors: Thelma R
authors: TR
authors: Cowley
authors: Marina
authors: M
authors: Lynch
authors: Michael G
authors: MG
authors: Stewart
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D056654:CA3 Region, Hippocampal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D008854:Microscopy, Electron; D019006:Neural Cell Adhesion Molecules / Q000008:administration & dosage / Q000494:pharmacology*; D009457:Neuroglia / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D016708:Synaptophysin / Q000096:biosynthesis*
chemical_list: D015703:Antigens, CD; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D005904:Glial Fibrillary Acidic Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C488618:NCAM protein (681-695), human; D019006:Neural Cell Adhesion Molecules; D016708:Synaptophysin; C042739:antigens, CD200