Unrevealing the neurophysiological mechanisms responsible for OWA induced behavioral changes in polar fish: an NMR approach

Applicant

Dr. Felizitas Charlotte Wermter
Universität Bremen
Fachbereich 2 (Chemie/Biologie)
Forschungsgruppe in-vivo-MR

Project Description 

The most dramatic impacts of climate change are expected for the polar regions, i. e. polar organisms are particularly affected by temperature and CO2 changes. In contrast to most marine invertebrates, fish have the ability to effectively regulate acid-bases. Nevertheless, neurological disturbances under increased CO2 concentrations could be detected for different species. However, the mechanisms underlying the CO2-induced behavioral changes and the extent to which Antarctic fish species are also affected have not yet been clarified.In first studies, a change in the reaction of the GABAA-receptor as well as in the GABA metabolism were postulated as possible causes. Furthermore, a decrease of the intracellular pH value (pHi) under hypercapnia could be shown in the brain of an Antarctic fish species. However, it has not yet been clarified whether one factor alone or a combination and interaction of different factors are responsible for the behavioral changes. Therefore, the non-invasive, spatially and temporally highly resolved determination of metabolite concentrations and pHi in vivo in the brain of polar fish will be of great importance for the understanding of neurological effects.The aim of this project is to gain a better understanding of the underlying mechanisms of neurological disorders in polar fish using new methodical approaches of localized in vivo 1H NMR spectroscopy. In particular, editing techniques will be used that allow a spectral simplification of the in vivo 1H NMR spectra by suppressing unwanted signals during acquisition. These approaches are already partially established in preclinical research but have to be adapted for special application to non-anesthetized polar fish (temperature around freezing point, movement, salt water, etc.). Furthermore, these methods will be combined with spectroscopic imaging techniques and the quantification of the 1H NMR spectra for polar temperatures will be optimized.In an earlier project, I and my colleagues used the Chemical Shift Saturation Transfer (CEST) approach for the first time for pH imaging on polar cod. We were able to show that TauCEST, i. e. the taurine-based CEST MRI, enables the determination of relative pHi changes with high spatial and temporal resolution in fish brain under elevated CO2 concentrations. According to current knowledge, an adaptation of this method for different polar fish species seems to be feasible.Therefore, the combination of localized in vivo 1H NMR spectroscopy and CEST MRI will allow the simultaneous quantification of metabolites and the determination of pHi with high spatial and temporal resolution to reveal the neurophysiological mechanisms responsible for the behavioral changes in polar fish observed under climate change scenarios.

DFG Programme: Infrastructure Priority Programmes

term since 2019