Epithelial Sodium Channels in the Brain: Effect of High Salt Diet on Their Expression

Epithelial Sodium Channels in the Brain: Effect of High Salt Diet on Their Expression

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dc.contributor.author Amin, Md. Shahrier
dc.date.accessioned 2011-06-28T15:05:38Z
dc.date.available 2011-06-28T15:05:38Z
dc.date.created 2011 en_US
dc.date.issued 2011-06-28
dc.identifier.uri http://hdl.handle.net/10393/20074
dc.description.abstract Statement of the problem: The epithelial sodium channels (ENaC) play an important role in regulation of blood pressure (BP). Although the genes are identical in Dahl salt sensitive (S) and Dahl salt resistant (R) rats, expression of ENaC subunits is increased in kidneys of S rats on high salt diet. Intracerebroventricular (icv) infusion of ENaC blocker benzamil prevents Na+ induced hypertension. It was not known whether ENaC subunits are expressed in the brain and whether or not brain ENaC plays a role in regulation of [Na+] in CNS. Hypothesis: 1. Epithelial sodium channels are expressed in the brain. 2. Expression of ENaC is increased in the kidneys and brain of Dahl S rats on high salt diet. 3. ENaC in the brain contributes to regulation of [Na+] in the CSF and brain interstitium. Methods of investigation: We studied expression and distribution of the ENaC subunits and assessed the effects of icv infusion of Na+-rich aCSF in Wistar rats or high salt diet in Dahl S rats in different areas of the brain. Function of ENaC in the choroid plexus was evaluated by studying the effects of benzamil and ouabain on Na+ transport. Major findings: In Wistar rats, both mRNA and protein of all three ENaC subunits are expressed in brain epithelia and magnocellular neurons in the supraoptic (SON) and paraventricular (PVN) nucleus. ENaC abundance is higher on the apical versus basolateral membrane of choroid cells. Benzamil decreases Na+ influx into choroid cells by 20-30% and increases CSF [Na+] by ~8 mmol/L. Na+ rich aCSF increases apical membrane expression of βENaC in the choroid cells and of α and βENaC in basolateral membrane of ependymal cells, but has no effect on neuronal ENaC. Expression of ENaC is higher in choroid cells and SON of Dahl S versus R rats and the higher expression persists on a high salt diet. High salt attenuates the ouabain blockable efflux of Na+ from choroid cells and has no effect on CSF [Na+] in Dahl R rats. In contrast, high salt does not attenuate ouabain blockable efflux of 22Na+ and CSF [Na+] increases in Dahl S. Main Conclusion: ENaC in the brain contributes to Na+ transport into the choroid cells and appear to be involved in reabsorption of Na+ from the CSF. Aberrant regulation of Na+ transport and of Na+K+ATPase activity, might contribute to increases in CSF [Na+] in Dahl S rats on high-salt diet. ENaC in magnocellular neurons may contribute to enhanced secretion of mediators such as ‘ouabain’ leading to sympathetic hyperactivity in Dahl S rats. en_US
dc.language.iso en en_US
dc.subject Epithelial sodium channel en_US
dc.subject Brain en_US
dc.subject Kidney en_US
dc.subject Salt sensitive hypertension en_US
dc.subject Mineralocorticoid receptor en_US
dc.subject SGK1 en_US
dc.title Epithelial Sodium Channels in the Brain: Effect of High Salt Diet on Their Expression en_US
dc.type Thèse / Thesis en_US
dc.faculty.department Médecine cellulaire et moléculaire / Cellular and Molecular Medicine en_US
dc.contributor.supervisor Leenen, Frans H.
dc.embargo.terms immediate en_US
dc.degree.name phd en_US
dc.degree.level doctorate en_US
dc.degree.discipline Médecine / Medicine en_US

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