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

预计气候变化对极地地区的影响最为显著，即极地生物特别受温度和二氧化碳变化的影响。与大多数海洋无脊椎动物相比，鱼类具有有效调节酸碱的能力。然而，在二氧化碳浓度增加的情况下，可以检测到不同物种的神经紊乱。然而，二氧化碳引起的行为变化背后的机制以及南极鱼类受到影响的程度尚不清楚。在最初的研究中，gabaa受体的反应以及GABA代谢的变化被认为是可能的原因。此外，在高碳酸血症的情况下，一种南极鱼类的大脑可以显示出细胞内pH值（pHi）的降低。然而，目前尚不清楚是单一因素还是不同因素的组合和相互作用导致了行为变化。因此，非侵入性、空间和时间分辨率高的极地鱼类大脑体内代谢物浓度和pHi的测定对于了解神经学效应具有重要意义。这个项目的目的是为了更好地了解极地鱼类神经系统疾病的潜在机制，使用新的方法来定位体内1H核磁共振波谱。特别是，编辑技术将用于通过在采集过程中抑制不需要的信号来简化体内1H NMR光谱。这些方法已经部分建立在临床前研究中，但必须适应于非麻醉极地鱼的特殊应用（冰点附近的温度，运动，盐水等）。此外，这些方法将与光谱成像技术相结合，优化极性温度的1H NMR光谱定量。在早期的一个项目中，我和我的同事首次使用化学位移饱和转移（CEST）方法对极地鳕鱼进行pH成像。我们能够证明TauCEST，即基于牛磺酸的CEST MRI，能够以高空间和时间分辨率确定二氧化碳浓度升高时鱼脑中的相对pHi变化。根据目前的知识，将这种方法应用于不同的极地鱼类似乎是可行的。因此，将体内局部1H NMR波谱与CEST MRI相结合，可以同时定量测定代谢物和高时空分辨率的pHi，揭示气候变化情景下极地鱼类行为变化的神经生理机制。

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.