Microstructural effects of a neuro-modulating drug evaluated by diffusion tensor imaging

• Published in: NeuroImage (Orlando, Fla.) Fla.), 2016-02, Vol.127, p.1-10
• Main Authors: Egger, K., Janz, P., Döbrössy, M.D., Bienert, T., Reisert, M., Obmann, M., Glauche, V., Haas, C., Harsan, L.A., Urbach, H., von Elverfeldt, D.
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Animals; Axial diffusivity; Behavior; Body temperature; Brain; Brain - drug effects; BrdU; Cell growth; Cell Proliferation - drug effects; Corpus callosum; DCX; Dentate gyrus; Diffusion; Diffusion Tensor Imaging; DTI; EPO; Erythropoietin; Erythropoietin - pharmacology; Fractional anisotropy; Hippocampus; Hypotheses; Image Processing, Computer-Assisted; Immunohistochemistry; Kinases; Learning; Longitudinal Studies; Male; Maze Learning - drug effects; Mean diffusivity; Mice; Mice, Inbred C57BL; Morris water maze; Mouse; MRI; Neurogenesis; Neuromodulation; NG2; NMR; Nuclear magnetic resonance; Physiology; Radial diffusivity; Respiration; Rodents; Studies; Trace; White matter
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2015.10.091

In a longitudinal mouse study we evaluated whether diffusion tensor imaging (DTI) can monitor microstructural changes after administration of the neuromodulating drug EPO and whether erythropoietin (EPO) has an effect on cognitive performance. Twelve mice (2 groups with 6 mice each) were scanned in a 7T Bruker Biospin animal scanner with a highly resolved DTI sequence before and 16days after intraperitoneal injections of EPO or saline. All mice underwent behavioral testing (Morris water maze) and histologic evaluation of hippocampal and corpus callosum cell proliferation and oligodendrogenesis. Whole brain DTI analysis showed significant Trace, RD and AD decrease within the dentate gyrus, subiculum, primary motor, somatosensory, and supplementary somatosensory areas and FA increase in the hippocampus, corpus callosum, and fimbria fornix in EPO treated mice only. ROI-based DTI analysis showed significant Trace and RD decrease and FA increase only in the corpus callosum of EPO treated mice, whereas in the dentate gyrus significant Trace, RD, and AD decrease occurred in both, EPO- and control-group. Behavioral tests showed that EPO treated mice performed better and learned faster than controls. Histologically, the number of BrdU-positive nuclei and optical density of DCX-labeled juvenile neurons significantly increased within the dentate gyrus, corpus callosum and fimbria fornix and the number of NG2-positive oligodendrocyte progenitors in corpus callosum and fimbria fornix, respectively. In conclusion we were able to monitor microstructural changes with DTI and showed EPO treatment-related alterations correlating with enhanced dentate gyrus and corpus callosum cell proliferation and better learning capabilities. •This longitudinal mouse study revealed EPO related cerebral DTI changes.•We showed significant Trace, RD and AD decrease in white and gray matter structures.•After EPO administration there was significant FA increase in the corpus callosum.•EPO combined with learning results in enhanced neural cell proliferation.