Segmental aging underlies the development of a Parkinson phenotype in the AS/AGU rat

Khojah, S. M., Payne, A. P., McGuinness, D. and Shields, P. G. (2016) Segmental aging underlies the development of a Parkinson phenotype in the AS/AGU rat. Cells, 5(4), 38. (doi: 10.3390/cells5040038) (PMID:27763519) (PMCID:PMC5187522)

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Abstract

There is a paucity of information on the molecular biology of aging processes in the brain. We have used biomarkers of aging (SA β-Gal, p16Ink4a, Sirt5, Sirt6, and Sirt7) to demonstrate the presence of an accelerated aging phenotype across different brain regions in the AS/AGU rat, a spontaneous Parkinsonian mutant of PKCγ derived from a parental AS strain. P16INK4a expression was significantly higher in AS/AGU animals compared to age-matched AS controls (p < 0.001) and displayed segmental expression across various brain regions. The age-related expression of sirtuins similarly showed differences between strains and between brain regions. Our data clearly show segmental aging processes within the rat brain, and that these are accelerated in the AS/AGU mutant. The accelerated aging, Parkinsonian phenotype, and disruption to dopamine signalling in the basal ganglia in AS/AGU rats, suggests that this rat strain represents a useful model for studies of development and progression of Parkinson's disease in the context of biological aging and may offer unique mechanistic insights into the biology of aging.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McGuinness, Dr Dagmara and Payne, Professor Anthony
Authors: Khojah, S. M., Payne, A. P., McGuinness, D., and Shields, P. G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Cells
Publisher:MDPI
ISSN:2073-4409
ISSN (Online):2073-4409
Published Online:17 October 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Cells 5(4):38
Publisher Policy:Reproduced under a Creative Commons License

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