Brain Protein Behind High-Salt-Induced Hypertension and Cognitive Impairment

The aspects of high salt intake mediated hypertension and emotional/cognitive impairment were thoroughly assessed in a new study published in British Journal of Pharmacology. A team of collaborating researchers has shown how hypertension, mediated by the crosstalk between two key physiological systems cause emotional and cognitive dysfunction. Dementia is defined as the loss of cognitive functioning—including thinking, remembering, and reasoning—and is very prevalent in Japan. Currently, the treatment satisfaction for dementia is among the lowest and no drug therapy is available to cure the disease. With a rapidly aging global population, the development of dementia preventive and therapeutic drugs is critical.

Reviewing the Effects of Dietary Salt on Blood Pressure and Cognition

Cognitive impairment has been linked to the consumption of excess table salt, a ubiquitous food seasoning. High salt (HS) intake can also lead to hypertension. To prevent adverse health outcomes, the World Health Organization recommends limiting salt intake to less than 5 g per day.

The involvement of angiotensin II (Ang II)—a hormone that plays a key role in regulating blood pressure and fluid balance—and its receptor “AT1”, as well as that of the physiologically important lipid molecule prostaglandin E2 (PGE2 and its receptor “EP1” in hypertension and neurotoxicity is well-recognized (1^✔ ✔Trusted Source
Angiotensin II–Dependent Hypertension Requires Cyclooxygenase 1–Derived Prostaglandin E2 and EP1 Receptor Signaling in the Subfornical Organ of the Brain

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However, the involvement of these systems in HS-mediated hypertension and emotional/cognitive impairment remains elusive. In this new study, the addition of excessive phosphates to the protein “tau” is primarily responsible for these emotional and cognitive consequences.

The findings are particularly noteworthy because tau is a key protein of Alzheimers disease. The team first loaded laboratory mice with an HS solution (2% NaCl in drinking water) for 12 weeks and monitored their blood pressure.

The effects of HS intake on emotional/cognitive function and tau phosphorylation were also examined in two key areas of the mouse brain—the prefrontal cortex and the hippocampus. The brains of the experimental mice had several biochemical alternations.

At the molecular level, besides the addition of phosphates to tau, the researchers also observed a decrease in the phosphate groups linked to a key enzyme called “CaMKII”—a protein involved in brain signaling (2^✔ ✔Trusted Source
High salt induces cognitive impairment via the interaction of the angiotensin II-AT1 and prostaglandin E2-EP1 systems

Go to source).

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Moreover, changes in the levels of “PSD95”—a protein that plays a vital role in the organization and function of brain synapses (the connection between brain cells)—were also evident. Interestingly, the biochemical changes were reversed after the administration of the antihypertensive drug “losartan.” A similar reversal was observed after knocking out the EP1 gene.

Overall, these findings suggest that angiotensin II-AT1 and prostaglandin E2-EP1 systems could be novel therapeutic targets for hypertension-induced dementia.

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References:

1. Angiotensin II–Dependent Hypertension Requires Cyclooxygenase 1–Derived Prostaglandin E2 and EP1 Receptor Signaling in the Subfornical Organ of the Brain - (https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.111.182071)
2. High salt induces cognitive impairment via the interaction of the angiotensin II-AT1 and prostaglandin E2-EP1 systems - (https://bpspubs.onlinelibrary.wiley.com/doi/epdf/10.1111/bph.16093)

Source-Eurekalert