Effects of dietary salt on gene and protein expression in brain tissue of a model of sporadic small vessel disease

Bailey, E. , McBride, M. W. , McClure, J. D. , Beattie, W., Graham, D. , Dominiczak, A. , Smith, C. and Wardlaw, J. (2018) Effects of dietary salt on gene and protein expression in brain tissue of a model of sporadic small vessel disease. Clinical Science, 132(12), pp. 1315-1328. (doi: 10.1042/CS20171572) (PMID:29632138) (PMCID:PMC6365623)

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Background: The effect of salt on cerebral small vessel disease (SVD) is poorly understood. We assessed the effect of dietary salt on the cerebral tissue of the strokeprone spontaneously hypertensive rat (SHRSP) - a relevant model of sporadic SVD - at both the gene and protein level. Methods: Brains from 21 week old SHRSP and Wistar-Kyoto rats, half additionally salt-loaded (via a 3 week regime of 1% NaCl in drinking water) were split into 2 hemispheres and sectioned coronally – one hemisphere for mRNA microarray and qRT-PCR, the other for immunohistochemistry using a panel of antibodies targeting components of the neurovascular unit. Results: We observed differences in gene and protein expression affecting the acute phase pathway and oxidative stress (ALB, AMBP, APOH, AHSG and LOC100129193, up-regulated in salt-loaded WKY versus WKY, >2-fold), active microglia (increased Iba-1 protein expression in salt-loaded SHRSP versus saltloaded WKY, p<0.05), vascular structure (ACTB & CTNNB, up-regulated in saltloaded SHRSP versus SHRSP, >3-fold; CLDN-11,VEGF and VGF downregulated >- 2-fold in salt-loaded SHRSP versus SHRSP) and myelin integrity (MBP downregulated in salt loaded WKY rats versus WKY, >2.5-fold). Changes of salt-loading were more pronounced in SHRSP and occurred without an increase in blood pressure in WKY rats. Conclusion: Salt exposure induced changes in gene and protein expression in an experimental model of SVD and its parent rat strain in multiple pathways involving components of the glio-vascular unit. Further studies in pertinent experimental models at different ages would help clarify the short and long-term effect of dietary salt in SVD.

Item Type:Articles
Additional Information:This work was supported by a Medical Research Council PhD studentship, the Newby Fund (University of Edinburgh) and the British Neuropathological Society (all for E.L.B.); the Scottish Funding Council through the SINAPSE Collaboration (Scottish Imaging Network, A Platform for Scientific Excellence, http://www.sinapse.ac.uk, J.M.W.); British Heart Foundation Chair and Programme grant funding [CH98001, RG/07/005] and EURATRANS which is co-funded by the European Community’s Seventh Framework Programme [FP7/2007-2013] under grant agreement No. HEALTH-F4-2010-241504. Funding is gratefully acknowledged from the European Union Horizon 2020, PHC-03-15, project No 666881, ‘SVDs@Target’, and the Fondation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease, ref no. 16 CVD 05.
Glasgow Author(s) Enlighten ID:Graham, Dr Delyth and McBride, Dr Martin and Beattie, Mrs Wendy and Bailey, Dr Emma and Dominiczak, Professor Anna and McClure, Dr John
Authors: Bailey, E., McBride, M. W., McClure, J. D., Beattie, W., Graham, D., Dominiczak, A., Smith, C., and Wardlaw, J.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Clinical Science
Publisher:Portland Press
ISSN (Online):1470-8736
Published Online:09 April 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Clinical Science 132(12):1315-1328
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
464051Genomics and proteomics of hypertension and its vascular complications: the pathwayomic strategies.Anna DominiczakBritish Heart Foundation (BHF)RG/07/005/23633RI CARDIOVASCULAR & MEDICAL SCIENCES
515251EuratransAnna DominiczakEuropean Commission (EC)241504RI CARDIOVASCULAR & MEDICAL SCIENCES