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J Neuropathol Exp Neurol. 2016 May;75(5):464-78. doi: 10.1093/jnen/nlw019. Epub 2016 Mar 30.

A Neurogenic Perspective of Sarcopenia: Time Course Study of Sciatic Nerves From Aging Mice.

Author information

1
From the School of Anatomy, Physiology and Human Biology (VSK, ZW, SIH, TS, ARH, MDG) and Experimental and Regenerative Neurosciences (SIH, ARH, MG), School of Animal Biology (MF), The University of Western Australia, Perth, Western Australia, Australia; Developmental Biology Group, AgResearch Ltd., Hamilton, New Zealand (CDM); Western Australian Neuroscience Research Institute, Perth, Western Australia, Australia (ARH, SIH); Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia and Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia (ZW).
2
From the School of Anatomy, Physiology and Human Biology (VSK, ZW, SIH, TS, ARH, MDG) and Experimental and Regenerative Neurosciences (SIH, ARH, MG), School of Animal Biology (MF), The University of Western Australia, Perth, Western Australia, Australia; Developmental Biology Group, AgResearch Ltd., Hamilton, New Zealand (CDM); Western Australian Neuroscience Research Institute, Perth, Western Australia, Australia (ARH, SIH); Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia and Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia (ZW). miranda.grounds@uwa.edu.au.

Abstract

To elucidate the neural basis for age-related sarcopenia, we quantified morphologic and molecular changes within sciatic nerves of aging male and female C57BL/6J mice aged between 3 and 27 months using immunoblotting, immunohistochemistry, and electron microscopy. Protein analyses by immunoblotting of nerves of male mice aged 4, 15, 18, 22, and 24 months showed increased levels of heavy chain SMI-32-positive neurofilaments, vimentin, tau5, choline acetyltransferase (ChAT), and p62 by 18-22 months. Similar protein increases were seen in 26-month-old compared with 3-month-old female mice. Immunostaining of longitudinal sections of old (27-month-old) male sciatic nerves revealed intense staining for tau5 and p62 that was increased compared with that at 3 months, but there were decreased numbers of axon profiles stained for ChAT or isolectin B4 (motor and sensory axons, respectively). Ultrastructural analysis revealed electron-dense aggregates within axons in peripheral nerves of old male mice; the proportion of axons that contained aggregates more than doubled between 15 and 27 months. Overall, the observed age-related accumulation of many proteins from about 18 months of age onward suggests impaired mechanisms for axonal transport and protein turnover. These peripheral nerve changes may contribute to the morphological and functional muscle deficits associated with sarcopenia.

KEYWORDS:

Aging; Autophagy; Axonal proteins; Peripheral nerve; Protein aggregation; Sarcopenia.

PMID:
27030741
DOI:
10.1093/jnen/nlw019
[Indexed for MEDLINE]
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