Age-related decrease in axonal transport measured by MR imaging in vivo

Washington National Regional Primate Center, Washington, USA.
NeuroImage (Impact Factor: 6.36). 03/2008; 39(3):915-26. DOI: 10.1016/j.neuroimage.2007.08.036
Source: PubMed


Axonal transport is a crucial process for neuronal homeostasis and cell functions. In vitro studies have indicated transport rates decrease with age. Disruption of axonal transport has been implicated in age-associated neurodegenerative disorders. We hypothesized that aged rats would show decreased transport in the brain, which could be measured using in vivo manganese-enhanced MR imaging (Mn-MRI) and parametric estimation. Serial T1-weighted images were obtained at pre- and post-administration of MnCl(2) in rats scanned longitudinally (n=4) and in a separate aged group (n=3). Subtraction analysis was performed for group-wise statistical comparison on a pixel-by-pixel basis. Change in intensity over time was plotted for the olfactory bulb and anterior and posterior olfactory tract. Bulk transport of material was estimated over an initial 72 h. Tracer kinetic estimation of time-intensity data, based on a mass transport model, used intensity change in the bulb as input function for subsequent changes in the tract. Time to the peak of Mn(2+) flow was estimated for both anterior and posterior tracts. Results indicated age-related decreases in axonal transport rate and bulk transport of material in the olfactory tract of living rat brains. Longitudinally scanned, mid-age group was decreased by 58% and the aged group by 71% of young rate (neuronal transport=4.07+/-1.24 mm/h, 1.72+/-0.89 mm/h, and 1.16+/-0.18 mm/h for young, mid-age, and aged, respectively). Neuronal transport rate decreases correlated with increased age. The use of kinetic analysis combined with dynamic manganese enhanced MR imaging provides a unique opportunity to study this important neuronal process.

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Available from: Donna J Cross, Aug 18, 2015
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    • "Fundamental axonal pathology in AD includes the aberrant accumulation of various proteins in abnormal swollen axons, including APP (Cras et al., 1991), synaptic proteins like alpha-synuclein (Wirths et al., 2000), glycogen (Mann et al., 1987), as well as the occurrence of abnormal paired helical filaments (PHFs) (Praprotnik et al., 1996). With the implementation of new imaging techniques, it has been recently shown in in-vivo studies that impairment of axonal transport mechanisms and decreased axonal transport rates might have a significant impact on the pathogenesis of AD already early in the disease process (Smith et al., 2003; Teipel et al., 2007; Cross et al., 2008; Minoshima and Cross, 2008). "
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    • "2D and 3D). These differences highlight the advantages afforded by the acquisition of the long time-frame protocol we used, which gives access to all parameters of manganese transport (Cross et al., 2008). In contrast, short time-frame protocols are more widely used in mice, less time-consuming, and do not require any image registration; but they are limited to the analysis of an anatomical region predefined experimentally using a single parameter, the slope of manganese progression (Kim et al., 2011; Massaad et al., 2010; Smith et al., 2007, 2010a). "
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