Selenoprotein P deletion ameliorates metabolic stress-associated anxiety-like behavior in male mice

TL;DR

Deleting selenoprotein P in mice brains reduced anxiety-like behavior linked to metabolic stress, suggesting a new connection between metabolism and anxiety.

Contribution

The study identifies selenoprotein P as a potential link between metabolic stress and anxiety in mice.

Findings

Selenop is produced by glial and endothelial cells in the brain.

Deleting Selenop in mice brains reduced anxiety-like behavior under high-fat diet conditions.

Higher serum selenoprotein P levels were found in people with anxiety symptoms.

Abstract

Diabetes-associated metabolic stress and anxiety reciprocally influence one another's onset and course. We previously linked excessive selenoprotein P (SeP, encoded by SELENOP in humans) to pathological conditions frequently observed in individuals with diabetes.

The present study aimed to clarify the role of SeP in the metabolic stress-induced anxiety.

We visualized Selenop expression in the mouse brain section via RNAscope in situ hybridization and used RT-qPCR to evaluate gene expression in brain regions. We created brain-specific Selenop knockout (bSelenop-/-) mice by mating Selenop-flox and Nestin-Cre mice and conducted behavior tests for anxiety-like behavior and spatial memory under both a standard (STD) and high-fat, high-sucrose diet (HFHSD) conditions. In a cross-sectional general population cohort study, we examined differences in serum selenoprotein P concentrations between individuals with and without anxiety symptoms.

RNAscope in situ hybridization identified glial and endothelial cells as the sources of SeP synthesis in the brain. Selenop was expressed at the same level in the brains of mice fed with an STD and HFHSD. bSelenop-/- mice did not exhibit altered body weight or glucose tolerance associated with HFHSD feeding. High-fat, high-sucrose diet aggravated the anxiety-like behavior in the control mice, whereas Selenop deletion in the brain ameliorated the anxiety-like behavior without affecting spatial memory. Epidemiological data revealed that serum selenoprotein P was significantly higher in subjects with anxiety symptoms.

These findings suggest that excess SeP production may be a common trait linking metabolic stress with anxiety.

Figures