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Aging Does Not Affect Axon Initial Segment Structure and Somatic Localization of Tau Protein in Hippocampal Neurons of Fischer 344 Rats

Little is known about the specific contributions of aging to the neuron dysfunction and death in Alzheimer’s disease (AD). AD is characterized by the pathological accumulation of abnormal tau (a microtubule-associated protein), and the mislocalization of tau from the axon to the somatodendritic comp...

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Autores principales: Kneynsberg, Andrew, Kanaan, Nicholas M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520750/
https://www.ncbi.nlm.nih.gov/pubmed/28785724
http://dx.doi.org/10.1523/ENEURO.0043-17.2017
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author Kneynsberg, Andrew
Kanaan, Nicholas M.
author_facet Kneynsberg, Andrew
Kanaan, Nicholas M.
author_sort Kneynsberg, Andrew
collection PubMed
description Little is known about the specific contributions of aging to the neuron dysfunction and death in Alzheimer’s disease (AD). AD is characterized by the pathological accumulation of abnormal tau (a microtubule-associated protein), and the mislocalization of tau from the axon to the somatodendritic compartment is thought to play an important role in disease pathogenesis. The axon initial segment (AIS) is thought to play a role in the selective localization of tau in the axonal compartment. Thus, disruption in the AIS barrier may allow tau to diffuse freely back into the somatodendritic compartment and potentially lead to neurotoxicity. Here, we analyzed AISs using stereological methods and protein immunoblotting, and the localization of tau was assessed with immunofluorescence optical density measurements and protein immunoblotting. None of the outcome measurements assessed, including AIS structure, AIS protein levels, the distribution of tau in neurons of the hippocampus (HP), and total tau or phospho-tau protein levels were different in young, middle-, and old-age Fischer 344 rats. The outcome measurements assessed, including AIS structure, AIS protein levels, the distribution of tau in neurons of the HP, and total tau or phospho-tau protein levels were not different in young, middle-, and old-age Fischer 344 rats, with the exception of a small reduction in AIS volume and diameter in the CA2 region of aged animals. These data suggest that aging largely has no effect on these properties of the AIS or tau distribution, and thus, may not contribute directly to tau mislocalization.
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spelling pubmed-55207502017-08-07 Aging Does Not Affect Axon Initial Segment Structure and Somatic Localization of Tau Protein in Hippocampal Neurons of Fischer 344 Rats Kneynsberg, Andrew Kanaan, Nicholas M. eNeuro Negative Results Little is known about the specific contributions of aging to the neuron dysfunction and death in Alzheimer’s disease (AD). AD is characterized by the pathological accumulation of abnormal tau (a microtubule-associated protein), and the mislocalization of tau from the axon to the somatodendritic compartment is thought to play an important role in disease pathogenesis. The axon initial segment (AIS) is thought to play a role in the selective localization of tau in the axonal compartment. Thus, disruption in the AIS barrier may allow tau to diffuse freely back into the somatodendritic compartment and potentially lead to neurotoxicity. Here, we analyzed AISs using stereological methods and protein immunoblotting, and the localization of tau was assessed with immunofluorescence optical density measurements and protein immunoblotting. None of the outcome measurements assessed, including AIS structure, AIS protein levels, the distribution of tau in neurons of the hippocampus (HP), and total tau or phospho-tau protein levels were different in young, middle-, and old-age Fischer 344 rats. The outcome measurements assessed, including AIS structure, AIS protein levels, the distribution of tau in neurons of the HP, and total tau or phospho-tau protein levels were not different in young, middle-, and old-age Fischer 344 rats, with the exception of a small reduction in AIS volume and diameter in the CA2 region of aged animals. These data suggest that aging largely has no effect on these properties of the AIS or tau distribution, and thus, may not contribute directly to tau mislocalization. Society for Neuroscience 2017-07-21 /pmc/articles/PMC5520750/ /pubmed/28785724 http://dx.doi.org/10.1523/ENEURO.0043-17.2017 Text en Copyright © 2017 Kneynsberg and Kanaan http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Negative Results
Kneynsberg, Andrew
Kanaan, Nicholas M.
Aging Does Not Affect Axon Initial Segment Structure and Somatic Localization of Tau Protein in Hippocampal Neurons of Fischer 344 Rats
title Aging Does Not Affect Axon Initial Segment Structure and Somatic Localization of Tau Protein in Hippocampal Neurons of Fischer 344 Rats
title_full Aging Does Not Affect Axon Initial Segment Structure and Somatic Localization of Tau Protein in Hippocampal Neurons of Fischer 344 Rats
title_fullStr Aging Does Not Affect Axon Initial Segment Structure and Somatic Localization of Tau Protein in Hippocampal Neurons of Fischer 344 Rats
title_full_unstemmed Aging Does Not Affect Axon Initial Segment Structure and Somatic Localization of Tau Protein in Hippocampal Neurons of Fischer 344 Rats
title_short Aging Does Not Affect Axon Initial Segment Structure and Somatic Localization of Tau Protein in Hippocampal Neurons of Fischer 344 Rats
title_sort aging does not affect axon initial segment structure and somatic localization of tau protein in hippocampal neurons of fischer 344 rats
topic Negative Results
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520750/
https://www.ncbi.nlm.nih.gov/pubmed/28785724
http://dx.doi.org/10.1523/ENEURO.0043-17.2017
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