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

Abstract

Background: The effect of salt on cerebral small vessel disease (SVD) is poorly understood. We assessed the effect of dietary salt on cerebral tissue of the stroke-prone 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 two 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 salt-loaded WKY, p < 0.05), vascular structure (ACTB and CTNNB, up-regulated in salt-loaded SHRSP versus SHRSP, > 3-fold; CLDN-11, VEGF and VGF down-regulated > 2-fold in salt-loaded SHRSP versus SHRSP) and myelin integrity (MBP down-regulated 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.