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Up-regulation of Synaptotagmin IV within amyloid plaque-associated dystrophic neurons in Tg2576 mouse model of Alzheimer's disease.

Abstract：

AIM:To investigate the involvement of the vesicular membrane trafficking regulator Synaptotagmin IV (Syt IV) in Alzheimer's disease pathogenesis and to define the cell types containing increased levels of Syt IV in the β-amyloid plaque vicinity. METHODS:Syt IV protein levels in wild type (WT) and Tg2576 mice cortex were determined by Western blot analysis and immunohistochemistry. Co-localization studies using double immunofluorescence staining for Syt IV and markers for astrocytes (glial fibrillary acidic protein), microglia (major histocompatibility complex class II), neurons (neuronal specific nuclear protein), and neurites (neurofilaments) were performed in WT and Tg2576 mouse cerebral cortex. RESULTS:Western blot analysis showed higher Syt IV levels in Tg2576 mice cortex than in WT cortex. Syt IV was found only in neurons. In plaque vicinity, Syt IV was up-regulated in dystrophic neurons. The Syt IV signal was not up-regulated in the neurons of Tg2576 mice cortex without plaques (resembling the pre-symptomatic conditions). CONCLUSIONS:Syt IV up-regulation within dystrophic neurons probably reflects disrupted vesicular transport or/and impaired protein degradation occurring in Alzheimer's disease and is probably a consequence but not the cause of neuronal degeneration. Hence, Syt IV up-regulation and/or its accumulation in dystrophic neurons may have adverse effects on the survival of the affected neuron.

journal_name

Croat Med J

journal_title

Croatian medical journal

authors

Tratnjek L,Zivin M,Glavan G

doi

10.3325/cmj.2013.54.419

subject

Has Abstract

pub_date

2013-10-28 00:00:00

pages

419-28

issue

5

eissn

0353-9504

issn

1332-8166

journal_volume

54

pub_type

杂志文章

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