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Lookup NU author(s): Emma Robson, Clare Tweedy, Dr NELSON Manzanza, Professor John-Paul TaylorORCiD, Fiona Randall, Dr Amy Reeve, Dr Gavin ClowryORCiD, Dr Fiona LeBeauORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2018 IBRO Intracellular accumulation of alpha-synuclein (α-syn) is a key pathological process evident in Lewy body dementias (LBDs), including Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB). LBD results in marked cognitive impairments and changes in cortical networks. To assess the impact of abnormal α-syn expression on cortical network oscillations relevant to cognitive function, we studied changes in fast beta/gamma network oscillations in the hippocampus in a mouse line that over-expresses human mutant α-syn (A30P). We found an age-dependent reduction in the power of the gamma (20–80 Hz) frequency oscillations in slices taken from mice aged 9–16 months (9+A30P), that was not present in either young 2–6 months old (2+A30P) mice, or in control mice at either age. The mitochondrial blockers potassium cyanide and rotenone both reduced network oscillations in a concentration-dependent manner in aged A30P mice and aged control mice but slices from A30P mice showed a greater reduction in the oscillations. Histochemical analysis showed an age-dependent reduction in cytochrome c oxidase (COX) activity, suggesting a mitochondrial dysfunction in the 9+A30P group. A deficit in COX IV expression was confirmed by immunohistochemistry. Overall, our data demonstrate an age-dependent impairment in mitochondrial function and gamma frequency activity associated with the abnormal expression of α-syn. These findings provide mechanistic insights into the consequences of over-expression of α-syn which might contribute to cognitive decline.
Author(s): Robson E, Tweedy C, Manzanza N, Taylor J-P, Atkinson P, Randall F, Reeve A, Clowry GJ, LeBeau FEN
Publication type: Article
Publication status: Published
Journal: Neuroscience
Year: 2018
Volume: 377
Pages: 161-173
Print publication date: 01/05/2018
Online publication date: 07/03/2018
Acceptance date: 26/02/2018
Date deposited: 24/04/2018
ISSN (print): 0306-4522
ISSN (electronic): 1873-7544
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.neuroscience.2018.02.032
DOI: 10.1016/j.neuroscience.2018.02.032
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