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

Abstract：

:The impairment of axonal transport by overexpression or hyperphosphorylation of tau is well documented for in vitro conditions; however, only a few studies on this phenomenon have been conducted in vivo, using invasive procedures, and with contradictory results. Here we used the non-invasive, Manganese-Enhanced Magnetic Resonance Imaging technique (MEMRI), to study for the first time a pure model of tauopathy, the JNPL3 transgenic mouse line, which overexpresses a mutated (P301L) form of the human tau protein. We show progressive impairment in neuronal transport as tauopathy advances. These findings are further supported by a significant correlation between the severity of the impairment in neuronal transport assessed by MEMRI, and the degree of abnormal tau assessed by histology. Unlike conventional techniques that focus on axonal transport measurement, MEMRI can provide a global analysis of neuronal transport, i.e. from dendrites to axons and at the macroscopic scale of fiber tracts. Neuronal transport impairment has been shown to be a key pathogenic process in Alzheimer's disease and numerous other neurodegenerative disorders. Hence, MEMRI provides a promising set of functional biomarkers to be used during preclinical trials to facilitate the selection of new drugs aimed at restoring neuronal transport in neurodegenerative diseases.

journal_name

Neuroimage

journal_title

NeuroImage

authors

Bertrand A,Khan U,Hoang DM,Novikov DS,Krishnamurthy P,Rajamohamed Sait HB,Little BW,Sigurdsson EM,Wadghiri YZ

doi

10.1016/j.neuroimage.2012.08.065

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

693-702

eissn

1053-8119

issn

1095-9572

pii

S1053-8119(12)00874-9

journal_volume

64

pub_type

杂志文章

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