Monitoring brain disorders in glucocorticoid receptor-deficient zebrafish using ultrahigh field MRI
- 1. Institut für Analytische Chemie, Leipzig, Germany
- 2. Institute of Biology, Leiden, Netherlands
- 3. Institute of Medical Physics and Biophysics, Leipzig, Germany
- 4. Leiden Institute of Chemistry, Leiden, Netherlands
Introduction: The glucocorticoid receptor (GR) is a nuclear receptor which is expressed almost ubiquitously in the human body and it controls a wide range of biological processes including metabolism, immune response and brain function. The regulation of the production of glucocorticoid hormones in the zebrafish is similar to that in humans. Recently an adult viable zebrafish mutant with a glucocorticoid receptor deficiency (grs357) has been identified which displays a hyperactive hypothalamus-pituitary-interrenal (HPI) axis and increased depression-like behaviour in response to mild stress [1] . However, it is not clear whether the GR deficiency can cause any specific structural changes in the brain. In this study we have optimized and applied high resolution MRI methods to examine anatomical details in the brain of control and GR mutant zebrafish non-invasively.
Methods: Adult control and GR mutant (grs357) zebrafish, with a disruption in the transcriptional activity of GR were used. All MRI measurements were conducted on a 9.4T vertical bore system, using a transmit/receive birdcage radiofrequency coil with an inner diameter of 10 mm and a 1 Tm-1gradient insert (Bruker, Germany). T2- weighted MR images were acquired by RARE sequence: TE = 10.5 ms; TR = 5s; echo train length = 4; FOV = 1.2 cm2; resolution = 47 micrometer]. For relaxation time measurement, MSME sequence was used as described earlier [2] .
Results and conclusions: Optimized RARE sequence at 9.4T provided sufficient resolution to obtain anatomical details in both sagittal and coronal direction from adult zebrafish brains. Interestingly, the size of some of the brain structures including ventricles appeared larger in GR mutant fish than in control fish. Hyperintensities corresponding to fat signal were clearly higher in GR fish as also confirmed by optimized MSME sequence. These preliminary results suggest that lack of glucocorticoid signalling may be responsible for hypertrophy of some of the brain structures. Further studies using in vivo MRI and MR spectroscopy are underway to get insight into how a lack of GR signalling influences the metabolic crosstalk in the brain and its influence on overall structural changes in the brain.