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Changes in TDP-43 expression in development, aging, and in the neurofilament light protein knockout mouse

The transactive response DNA-binding protein 43 (TDP-43) has been identified as a neurofilament light (NF-L) mRNA binding protein. Abnormally increased levels of TDP-43 are detected in patients with amyotrophic lateral sclerosis as well as a downregulation of NF-L mRNA. However, links between NF-L and TDP-43 expression are unclear. In this study, we investigated whether the deficiency of NF-L protein can result in alterations in TDP-43 localisation or protein expression and whether this is altered with ageing. There was a significant increase in TDP-43 protein levels in the cortex and lumbar spinal cord in 12-month old NF-L knockout (KO) mice, compared to wild-type (WT) C57BL/6 mice. However, there was no difference in the phosphorylation of TDP-43 between WT and NF-L KO mice, nor abnormal mislocalisation of TDP-43 to the cytoplasm in NF-L KO animals. Our findings suggest that NF-L protein or mRNA may negatively affect the expression of TDP-43 in the central nervous system. However, altered phosphorylation of TDP-43 may be more highly associated with ageing than levels of TDP-43 expression.

History

Publication title

Neurobiology of Aging: Experimental and Clinical Research

Volume

36

Pagination

1151-1159

ISSN

0197-4580

Department/School

Wicking Dementia Research Education Centre

Publisher

Elsevier Science Inc

Place of publication

360 Park Ave South, New York, USA, Ny, 10010-1710

Rights statement

Copyright 2014 Elsevier

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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