Elsevier

NeuroImage

Volume 39, Issue 3, 1 February 2008, Pages 915-926
NeuroImage

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

https://doi.org/10.1016/j.neuroimage.2007.08.036Get rights and content

Abstract

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 MnCl2 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 Mn2+ 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.

Section snippets

MnCl2 administration and MR scanning

Four male young (4 months) and three aged breeder (24–25 months, Charles River Labs) Sprague-Dawley rats had free access to food and water and were kept on a normal 12-h light/dark cycle. All procedures were approved by the University of Washington Animal Care Committee. The four young rats were scanned on 2 separate occasions at 4 months old and 13 to 17 months old (9 to 13 months apart) for a longitudinal assessment of decreased transport. In addition, to control for potential confounding

Statistical mapping indicates Mn2+ transport differences with age

Group-wise pixel-by-pixel statistical mapping indicated age-related decreases in manganese transport to the olfactory tract both anterior and posterior regions. Peak z-values for both anterior and posterior VOIs were calculated across time points from 1 h to 48 h. Using the threshold Z = 4.0 as indicating significantly increased enhancement, the young group showed significant manganese transport through the posterior tract as early as 11–12 h (Z = 6.0 and Z = 4.7, for anterior and posterior,

Discussion

The results of this study indicated age-associated axonal transport deficits including longitudinal differences in living rat brains. Longitudinal decrease in brain axonal transport rates of aged rats has not been reported previously. Investigations of axonal transport in the brain are limited, in part due to the relative inaccessibility of living brain neuronal tracts and the technical challenges inherent in studying a dynamic, sub-cellular process. Axonal transport rates have been shown to

Acknowledgments

This study is supported in part by Washington Alzheimer Disease Research Center Pilot Research grant, Washington National Primate Research Center grant NCRR P51 RR000166-41, and NINDS RO1 NS045254-01.

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