Age-related axonal swellings precede other neuropathological hallmarks in a knock-in mouse model of Huntington's disease

NEUROBIOLOGY OF AGING

卷:35

Article

Marangoni, Martina¹  Adalbert, Robert²  Janeckova, Lucie²  Patrick, Jane²  Kohli, Jaskaren¹  Coleman, Michael P.²  Conforti, Laura¹ 

[1] Univ Nottingham, Sch Med, Sch Life Sci, Queens Med Ctr, Nottingham NG7 2UH, England

[2] Babraham Inst, Cambridge, England

关键词: Huntington's disease;    Axon pathology;    Yellow fluorescent protein;    R6/2;    HdhQ140;    Stria terminalis;    mHTT aggregates;    Axonal swelling;   

DOI  :  10.1016/j.neurobiolaging.2014.04.024

来源: Elsevier

【 摘 要 】

Axon degeneration precedes cell body death in many age-related neurodegenerative disorders, often determining symptom onset and progression. A sensitive method for revealing axon pathology could indicate whether this is the case also in Huntington's disease (HD), a fatal, devastating neurodegenerative disorder causing progressive deterioration of both physical and mental abilities, and which brain region is affected first. We studied the spatio-temporal relationship between axon pathology, neuronal loss, and mutant Huntingtin aggregate formation in HD mouse models by crossing R6/2 transgenic and HdhQ140 knock-in mice with YFP-H mice expressing the yellow fluorescent protein in a subset of neurons. We found large axonal swellings developing age-dependently first in stria terminalis and then in corticostriatal axons of HdhQ140 mice, whereas alterations of other neuronal compartments could not be detected. Although mutant Huntingtin accumulated with age in several brain areas, inclusions in the soma did not correlate with swelling of the corresponding axons. Axon abnormalities were not a prominent feature of the rapid progressive pathology of R6/2 mice. Our findings in mice genetically similar to HD patients suggest that axon pathology is an early event in HD and indicate the importance of further studies of stria terminalis axons in man. Crown Copyright (C) 2014 Published by Elsevier Inc. All rights reserved.

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