How is excessive salt consumption linked to high BP and cognitive disorders?

According to the published data, the addition of excessive phosphates to the protein “tau” is primarily responsible for this emotional and cognitive consequences. The findings are particularly noteworthy because tau is a key protein of the Alzheimer's 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,” explains Prof. Mouri. Next, they also studied the involvement of the Ang II-AT1 and PGE2-EP1 systems in the HS-induced hypertension and neuronal/behavioral impairment.

The results were remarkable and encouraging: 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. Moreover, changes in the levels of “PSD95”-a protein that plays a vital role in the organization and function of brain synapses (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.

Prof. Mouri concludes by saying, “This study is of particular social and economic importance because the annual social cost of dementia treatment in Japan is surging like never before”. Therefore, developing preventive and therapeutic drugs for dementia seems critical for Japan’s rapidly aging population.”

Reference:

Hisayoshi Kubota, Kazuo Kunisawa, Bolati Wulaer, Masaya Hasegawa, Hitomi Kurahashi, Takatoshi Sakata, Hiroyuki Tezuka, Masanori Kugita, Shizuko Nagao, Taku Nagai, Tomoyuki Furuyashiki, Shuh Narumiya, Kuniaki Saito, Toshitaka Nabeshima, Akihiro Mouri, Published: 19 April 2023 https://doi.org/10.1111/bph.16093.