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Project Facts

Project name: The health benefits of deuterium depletion on synaptic function, regional metabolism, and behaviour

Project acronym: AQUA SYNAPSE

Call: HORIZON-MSCA-SE-2021

Type of action: MSCA-RISE

Number: 101086453

Starting/Ending date: 01 January 2023- 30 December 2026

Budget: €763,600.00

OUR IDEA

The main idea of this project is to establish the mechanistic basis of the positive health effects of deuterium depleted water. The isotope content of drinking water has been shown to possibly have implications to many diseases. High concentrations of deuterium may induce mitochondrial dysfunction, and can even lead to cell death. However, lower concentrations (deuterium depleted water) appear to have positive effects in human health and seem to represent a safe intervention with few, if any, side effects – but remains unclear at what concentrations the positive metabolic and behavioral effects become apparent. It has become urgent to better understand the impacts of deuterium depleted water on brain and behavior at molecular level, since that companies in Europe are now selling deuterium depleted water at different concentrations to the public with multiple health claims, that mostly lack sound scientific basis or safety data. To study the matter in dept, the consortium will use state-of-art imaging techniques to measure regional metabolic fluxes in the body of (healthy individuals) animals through life, and deuterium depleted water at different concentrations will be administrated and studied in different periods of time. Moreover, the consortium will also examine how the deuterium depletion affects the behaviors of neurons in vitro, electrophysiological levels and impacts on their metabolism.

PROJECT STRUCTURE

WP1: Deuterium metabolic spectroscopy and Deuterium metabolic imaging

Task 1.1. Deuterium metabolic spectroscopy (DMS) in deuterium-depleted mouses.
Task 1.2 Deuterium MR-based imaging (DMI) in deuterium-depleted mouses.
Task 1.3 Functional Deuterium metabolic spectroscopy (DMS), MR-based imaging (DMI) and Carbon 13 imaging in rodent models of aging using the housing on waters with various deuterium content.
Task 1.4 Functional Deuterium metabolic spectroscopy (DMS), MR-based imaging (DMI) and Carbon 13 imaging in mouse models of gene – environment interaction predisposing to depression associated with metabolic syndrome.
Task 1.5 Imaging of deuterized drugs using optimized conditions in a clinical setting and comparison vs and Carbon 13 imaging.

WP2: Deuterium impacting excitatory/inhibitory (E/I) balance in a human neuronal network model system

Task 2.1 A study of concentrations of deuterium that are restoring E/I imbalance the glutamatergic and GABAergic network in a line of isogenic CRISPR/Cas9 KO cell lines for 5-HTT/SLC6A4, risk gene of metabolic syndrome/depression, and established markers of compromised plasticity and molecular effects of DDW (Deuterium Depleted Water).
Task 2.2 A study of concentrations of deuterium that are restoring E/I imbalance the glutamatergic and GABAergic network in a line of isogenic CRISPR/Cas9 KO cell lines for CDH13, risk gene of metabolic syndrome/depression, and established markers of compromised plasticity and molecular effects of DDW.
Task 2.3 A study of concentrations of deuterium that are restoring E/I imbalance the glutamatergic and GABAergic network in a line of isogenic CRISPR/Cas9 KO cell lines for ST3GAL3, risk gene of metabolic syndrome/ cognitive dysfunction , and established markers of compromised plasticity and molecular effects of DDW.

WP3: Evaluation of effects of deuterium depletion in animal models of metabolic syndrome

Task 3.1 Functional effects of various concentrations of Deuterium in mouse model of Western diet associated with 5-HTT/SLC6A4 genetic deficiency, and established markers of compromised plasticity and molecular effects of DDW, also in development.
Task 3.2 Functional effects of various concentrations of Deuterium in mouse model of depression /ADHD/ metabolic syndrome associated with CDH13 genetic deficiency, and established markers of compromised plasticity and molecular effects of DDW, also in development.
Task 3.3 Functional effects of various concentrations of Deuterium in mouse model depression / metabolic syndrome caused by chronic stress, and established markers of compromised plasticity and molecular effects of DDW, also in development.

WP4: Evaluation of impact deuterium depletion in animal models of aging

Task 4.1 Functional effects of various concentrations of Deuterium in rat model of aging with cognitive decline on metabolic measures and brain plasticity and genetic risk markers of metabolic dysfunction disorders.
Task 4.2 Functional effects of various concentrations of Deuterium on synaptic plasticity of the hippocampus in rat model of aging with cognitive decline and genetic risk markers of metabolic dysfunction disorders.
Task 4.3 Functional effects of various concentrations of Deuterium in mouse model of cognitive aging and genetic risk markers of metabolic dysfunction disorders.

WP5: Production of deuterium depleted and control water samples, control of deuterium content in experimental tissue

Task 5.1 Production of experimental water with defined deuterium content following experimental protocols. In addition, control water of a standard mineral content will be produced and delivered to the laboratories.
Task 5.2 A measurement of the end concentration of deuterium in tissue and liquids obtained from experimental subjects and animals will be provided, following previously established methodology.
Task 5.3 Documentation preparation for the use of DDW of newly defined parameters, in humans.
Task 5.4 Exploitation Plan.

WP6: Project Management, Dissemination Activities

Task 6.1 Project Management Plan will be prepared in the beginning of the project, summarizing all the required knowledge for the good management of the project (in terms of administrative forms, financial aspects, quality process). Data Management Plan will be elaborated and delivered by month M3.
Task 6.2 Dissemination and Communication Plans Dissemination and Communication Plans will be worked out, discussed and approved during first of meeting of the consortium, then submitted at mid-term stage with an update towards the project end.
Task 6.3 Professional development via exchange of staff. Professional training, sharing of knowledge and experience among project participants will be conducted in different ways: research-based training, industrial-based training and seminars which will be held at hosts.
Task 6.4 Dissemination of scientific results of the project will be published in scientific journals with a relevant impact factor, presented at several widely-recognized world conferences.

DELIVERABLES

D1.1 Reference onset of the optimized imaging conditions in rodent models with deutorized tracers
D2.1 Elaborated mechanism of action of deuterium on the GABA-ergic and glutamate-ergic balance in neurons with altered monoamine regulation
D3.1 Elaborated mechanisms of action of DDW on metabolic functions in rodent models of Western diet and stress
D2.4 Prototype of DDW product with desired/ required properties of improving metabolic functions
D3.1 Data Management Plan
D5.2 Dissemination and Communication Plan
D5.3 Progress Report
D6.1 1st Work Shop
D6.2 Mid Term Meeting
D6.3 2nd Work Shop
D6.4 3rd Work Shop
D6.5 Project Conference