Selenium is an essential trace element that is delivered to the brain by the selenium transport protein selenoprotein P (SEPP1), primarily by binding to its receptor low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2), at the blood-brain barrier. Selenium transport is required for several important brain functions, with transgenic deletion of either Sepp1 or Lrp8 resulting in severe neurological dysfunction and death in mice fed a selenium-deficient diet. Previous studies have reported that although feeding a standard chow diet can prevent these severe deficits, some motor coordination and cognitive dysfunction remain. Importantly, no single study has directly compared the motor and cognitive performance of the Sepp1 and Lrp8 knockout (KO) lines. Here, we report the results of a comprehensive parallel analysis of the motor and spatial learning and memory function of Sepp1 and Lrp8 knockout mice fed a standard mouse chow diet. Our results revealed that Sepp1 knockout mice raised on a selenium-replete diet displayed motor and cognitive function that was indistinguishable from their wild-type littermates. In contrast, we found that although Lrp8-knockout mice fed a selenium-replete diet had normal motor function, their spatial learning and memory showed subtle deficits. We also found that the deficit in baseline adult hippocampal neurogenesis exhibited by Lrp8-deficit mice could not be rescued by dietary selenium supplementation. Taken together, these findings further highlight the importance of selenium transport in maintaining healthy brain function. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
LDL-Receptor Related Proteins , Mice, Knockout , Selenium , Spatial Learning , Animals , Mice , Diet , Hippocampus/metabolism , LDL-Receptor Related Proteins/genetics , LDL-Receptor Related Proteins/metabolism , Maze Learning/physiology , Maze Learning/drug effects , Memory/physiology , Memory/drug effects , Selenium/administration & dosage , Selenium/deficiency , Selenium/pharmacology , Selenoprotein P/genetics , Selenoprotein P/metabolism , Spatial Learning/physiology , Spatial Learning/drug effects , Spatial Memory/physiology , Spatial Memory/drug effects
AIM: Extrahepatic biliary atresia is a rare disorder. This creates challenges in the quality and quantity of research conducted. This issue is exacerbated by the potential heterogeneity in the reported outcomes in research examining the management of biliary atresia. A core outcome set is required to standardise reporting on the management of biliary atresia in research, facilitate systematic reviews that include outcomes of greatest importance to patients and clinicians, and to evaluate the quality of the existing evidence base on the management of biliary atresia. METHODS: A list of all potential outcomes will be developed through a systematic review of the literature. This list will be refined through a three-stage Delphi approach, involving key stakeholders in the management of biliary atresia. This will include patients and their parents, clinicians, nurses and allied health professionals. In this way, outcomes will be prioritised into a set of consensus core outcomes. CONCLUSION: The development of a core outcome set in biliary atresia management is needed to guide future research and assist in evaluating the quality of existing research. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Children's Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC), Ref: HREC/20/QCHQ/62448. Results of the study will be published in an open access format.
Biliary Atresia , Child , Consensus , Delphi Technique , Humans , Outcome Assessment, Health Care , Research Design , Systematic Reviews as Topic
