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Amyloid-beta induced CA1 pyramidal cell loss in young adult rats is alleviated by systemic treatment with FGL, a neural cell adhesion molecule-derived mimeticPeptide

Corbett, Nicola J.; Gabbott, Paul L.; Klementiev, Boris; Davies, Heather A.; Colyer, Frances M.; Novikova, Tatiana and Stewart, Michael G. (2013). Amyloid-beta induced CA1 pyramidal cell loss in young adult rats is alleviated by systemic treatment with FGL, a neural cell adhesion molecule-derived mimeticPeptide. PLOS One, 8(8), article no. e71479.

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DOI (Digital Object Identifier) Link: https://doi.org/10.1371/journal.pone.0071479
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Abstract

Increased levels of neurotoxic amyloid-beta in the brain are a prominent feature of Alzheimer’s disease. FG-Loop (FGL), a neural cell adhesion molecule-derived peptide that corresponds to its second fibronectin type III module, has been shown to provide neuroprotection against a range of cellular insults. In the present study impairments in social recognition memory were seen 24 days after a 5 mg/15 µl amyloid-beta(25–35) injection into the right lateral ventricle of the young adult rat brain. This impairment was prevented if the animal was given a systemic treatment of FGL. Unbiased stereology was used to investigate the ability of FGL to alleviate the deleterious effects on CA1 pyramidal cells of the amyloid-beta(25–35) injection. NeuN, a neuronal marker (for nuclear staining) was used to identify pyramidal cells, and immunocytochemistry was also used to identify inactive glycogen synthase kinase 3beta (GSK3β) and to determine the effects of amyloid-beta(25–35) and FGL on the activation state of GSK3β, since active GSK3β has been shown to cause a range of AD pathologies. The cognitive deficits were not due to hippocampal atrophy as volume estimations of the entire hippocampus and its regions showed no significant loss, but amyloid-beta caused a 40% loss of pyramidal cells in the dorsal CA1 which was alleviated partially by FGL. However, FGL treatment without amyloid-beta was also found to cause a 40% decrease in CA1 pyramidal cells. The action of FGL may be due to inactivation of GSK3β, as an increased proportion of CA1 pyramidal neurons contained inactive GSK3β after FGL treatment. These data suggest that FGL, although potentially disruptive in nonpathological conditions, can be neuroprotective in disease-like conditions.

Item Type: Journal Item
Copyright Holders: 2013 Corbett et al.
ISSN: 1932-6203
Project Funding Details:
Funded Project NameProject IDFunding Body
High resolution 3-D reconstructions from brain tissue via Field Emission scanning electron microscopy in back scattered electron (BSE) imaging modeBB/I020330/1BBSRC (Biotechnology and Biological Sciences Research Council)
Extra Information: 11 pp.
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 38177
Depositing User: Michael Stewart
Date Deposited: 15 Aug 2013 08:53
Last Modified: 07 Dec 2018 16:34
URI: http://oro.open.ac.uk/id/eprint/38177
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