Non-invasive, in vivo monitoring of neuronal transport impairment in a mouse model of tauopathy using MEMRI

Bertrand, Anne, et al. "Non-invasive,< i> in vivo monitoring of neuronal transport impairment in a mouse model of tauopathy using MEMRI." NeuroImage 64 (2013): 693-702. The tau protein is a well define protein involved in the stability of microtubules, found mainly in the axonal compartment of neurons. Unfortunately, under certain disease states referred to as tauopathies, such as Alzheimer's disease, there is a dysfunction in the tau protein due to over expression or increased phosphorylation that leads to aggregated tau protein. This tau protein aggregation is thought to blunt microtubule stabilization found under normal conditions and cause impairment of axonal transport, further leading to synaptic dysfunction. Previous to this study, the only methods used to examine axonal transport were either invasive in vivo techniques or in vitro techniques that came with many limitations. Anne Bertrand et. al, were interested in developing manganese enhanced MRI (MEMRI) as a non-invasive, in vivo technique that would allow for the observation of axonal transport viability under normal and tauopathy conditions. To do this a cross section study was done with both transgenic (tau pathology) and control mice, each population were injected intranasally with 1.5ul of 5M manganese chloride and groups were imaged at 3, 6, and 9 months at 1, 4, 8, 12, 24, 36, 48hrs, and 7-10 days following the injection. Each cohort was then sacrificed and used for immunhistochemistry examining tau protein concentrations. What Bertrand found was that there were significant decreases in MnCl2 signal propagation between WT and transgenic mice at 6 months in age in two tissue layers throughout the olfactory track that were examined (glomerular and mitral cell layers). There was also a significant decreases in signal propagation due to age between the transgenic mice 3 months of age and 6 months of age within the glomerular and mitral cell layer (smaller differences seen in the mitral cell layer). After immunohistochemistry, they were then able to correlate tau pathology to the observed MEMRI parameters. In this case, there was a significant negative correlation between tau pathology and signal propagation of manganese. Correspondingly, there was a greater correlation to dendritic tau staining and the MEMRI parameters compared to somatic tau staining and MEMRI parameters. Interestingly, this paper also did GFAP staining for astrogliosis to rule out differences in manganese accumulation from discrepancies in astroglial cells. They found no differences between GFAP staining in the WT and transgenic mice. Conclusively, this study demonstrated that MEMRI can be used as a viable in vivo technique for the analysis of axonal transport function, which may possibly be used for clinical analysis of tau protein as a biomarker for many disease states or possibly treatment options. ~JI