High salt induced hypertension leads to cognitive defect

Abstract

Although increasing evidences suggest a relationship between hypertension and brain function for years, it is still unclear whether hypertension constitutes a risk factor for cognitive decline and its underlying mechanism. In the present study, an experimental animal model of hypertension simply by feeding rats with high salt diet was employed. We found that long-term high salt intake caused a marked increase of systolic blood pressure linked to a declined regional cerebral blood flow. Fear conditioning and morris water maze behavioral test revealed that high salt diet induced hippocampal dependent spatial reference memory deficits, while a decreased synaptogenesis without neuronal loss in hippocampus was observed in high salt treated rats. Furthermore, we found that high salt induced a decrease of intracellular calcium, which inactivated CaMK II and resulted in dephosphorylation of CREB at Ser133. These findings suggest a novel etiopathogenic mechanism of cognitive deficit induced by hypertension, which is initiated by high salt diet.

Cerebral Fructose Metabolism as a Potential Mechanism Driving Alzheimer’s Disease

“…High salt diets are now being linked with dementia. High salt diets initially stimulate exploratory behavior in mice, but later it leads to a reduction in the short term and long-term memory with oxidative stress to the hypothalamus (Liu et al, 2014 ; Ge et al, 2017 ; Guo et al, 2017 ) that tends to be worse in older animals (Chugh et al, 2013 ). Moreover, a high salt diet induces hyperphosphorylation of tau protein in the hypothalamus (Faraco et al, 2019 ).…”

A High-Salt Diet Promotes Phosphorylated Tau and Cognitive Decline in Mice

“…A critical third variable is obesity, which is associated with both hypertension 39 and cognitive decline. 40 Yet, as for hypertension, most rodent studies reviewed here have found no effects of salt on body weight gain, 26,[28][29][30] with two exceptions reporting increased 16 and decreased weight 27 in high-salt groups relative to controls. Clearly, further work is required to delineate the effects of salt on the triad of body weight, hypertension, and cognition.…”

“…10 In rodent studies, even the salt content contained in control diets (typically between 0.3 and 0.5%) may be well above biological needs, given evidence that rats ingest only 15% of this amount when allowed to freely consume a 0.5% NaCl solution alongside a salt-free solid diet and water. 38 A second consideration is that in some rodent studies, high-salt diets have produced cognitive impairments without altering blood pressure, 26,27,30 whereas others have shown cognitive deficits alongside hypertension 28,29 (Ta- Figure 1. Overview of evidence for adverse effects of salt intake on cognition and other health outcomes.…”

Gradual hypertension induction in middle‐aged Cyp1a1‐Ren2 transgenic rats produces significant impairments in spatial learning

“…In addition to hypertension and upregulation of the renin angiotensin system, systemic inflammation secondary to target organ damage have each been associated with impaired cognitive function (Guo et al. ; Yamanaka et al. ; Ahmed et al.…”