A novel role for the immunophilin FKBP52 in motor coordination

FKBP52 is a ubiquitously distributed immunophilin that has been associated with wideranging functions in cell signalling as well as hormonal and stress responses. Amongst other pathways, it acts via complex-formation with corticosteroid receptors and has consequently been associated with stress- and...

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Main Authors: Young, Matthew J., Geiszler, Philippine C., Pardon, Marie-Christine
Format: Article
Published: Elsevier 2016
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Online Access:https://eprints.nottingham.ac.uk/35005/
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author Young, Matthew J.
Geiszler, Philippine C.
Pardon, Marie-Christine
author_facet Young, Matthew J.
Geiszler, Philippine C.
Pardon, Marie-Christine
author_sort Young, Matthew J.
building Nottingham Research Data Repository
collection Online Access
description FKBP52 is a ubiquitously distributed immunophilin that has been associated with wideranging functions in cell signalling as well as hormonal and stress responses. Amongst other pathways, it acts via complex-formation with corticosteroid receptors and has consequently been associated with stress- and age-related neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases. Reduced levels of FKBP52 have been linked to tau dysfunction and amyloid beta toxicity in AD. However, FKBP52’s role in cognition and neurodegenerative disorder-like phenotypes remained to be elucidated. The present study aimed therefore at investigating the cognitive and behavioural effects of reduced FKBP52 levels of genetically modified mice during ageing. Female and male FKBP52+/+, FKBP52+/- and FKBP52-/- mice were compared at two-, ten-, twelve-, fifteenand eighteen-months-of-age in a series of behavioural tests covering specie-specific behaviour, motor activity and coordination, fear-, spatial and recognition memory as well as curiosity and emotionality. Whilst cognitively unimpaired, FKBP52+/- mice performed worse on an accelerating rotating rod than FKBP52+/+ littermates across all age-groups suggesting that FKBP52 is involved in processes controlling motor coordination. This deficit did not exacerbate with age but did worsen with repeated testing; pointing towards a role for FKBP52 in learning of tasks requiring motor coordination abilities. This study contributes to the knowledge base of FKBP52’s implication in neurodegenerative diseases by demonstrating that FKBP52 by itself does not directly affect cognition and may therefore rather play an indirect, modulatory role in the functional pathology of AD, whereas it directly affects motor coordination, an early sign of neurodegenerative damages to the brain.
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spelling nottingham-350052020-05-04T18:02:29Z https://eprints.nottingham.ac.uk/35005/ A novel role for the immunophilin FKBP52 in motor coordination Young, Matthew J. Geiszler, Philippine C. Pardon, Marie-Christine FKBP52 is a ubiquitously distributed immunophilin that has been associated with wideranging functions in cell signalling as well as hormonal and stress responses. Amongst other pathways, it acts via complex-formation with corticosteroid receptors and has consequently been associated with stress- and age-related neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases. Reduced levels of FKBP52 have been linked to tau dysfunction and amyloid beta toxicity in AD. However, FKBP52’s role in cognition and neurodegenerative disorder-like phenotypes remained to be elucidated. The present study aimed therefore at investigating the cognitive and behavioural effects of reduced FKBP52 levels of genetically modified mice during ageing. Female and male FKBP52+/+, FKBP52+/- and FKBP52-/- mice were compared at two-, ten-, twelve-, fifteenand eighteen-months-of-age in a series of behavioural tests covering specie-specific behaviour, motor activity and coordination, fear-, spatial and recognition memory as well as curiosity and emotionality. Whilst cognitively unimpaired, FKBP52+/- mice performed worse on an accelerating rotating rod than FKBP52+/+ littermates across all age-groups suggesting that FKBP52 is involved in processes controlling motor coordination. This deficit did not exacerbate with age but did worsen with repeated testing; pointing towards a role for FKBP52 in learning of tasks requiring motor coordination abilities. This study contributes to the knowledge base of FKBP52’s implication in neurodegenerative diseases by demonstrating that FKBP52 by itself does not directly affect cognition and may therefore rather play an indirect, modulatory role in the functional pathology of AD, whereas it directly affects motor coordination, an early sign of neurodegenerative damages to the brain. Elsevier 2016-07-11 Article PeerReviewed Young, Matthew J., Geiszler, Philippine C. and Pardon, Marie-Christine (2016) A novel role for the immunophilin FKBP52 in motor coordination. Behavioural Brain Research, 313 . pp. 97-110. ISSN 1872-7549 FKBP52; behaviour; cognition; rotarod; motor coordination http://www.sciencedirect.com/science/article/pii/S0166432816304430 doi:10.1016/j.bbr.2016.07.015 doi:10.1016/j.bbr.2016.07.015
spellingShingle FKBP52; behaviour; cognition; rotarod; motor coordination
Young, Matthew J.
Geiszler, Philippine C.
Pardon, Marie-Christine
A novel role for the immunophilin FKBP52 in motor coordination
title A novel role for the immunophilin FKBP52 in motor coordination
title_full A novel role for the immunophilin FKBP52 in motor coordination
title_fullStr A novel role for the immunophilin FKBP52 in motor coordination
title_full_unstemmed A novel role for the immunophilin FKBP52 in motor coordination
title_short A novel role for the immunophilin FKBP52 in motor coordination
title_sort novel role for the immunophilin fkbp52 in motor coordination
topic FKBP52; behaviour; cognition; rotarod; motor coordination
url https://eprints.nottingham.ac.uk/35005/
https://eprints.nottingham.ac.uk/35005/
https://eprints.nottingham.ac.uk/35005/