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Transcriptome and methylome of the supraoptic nucleus provides insights into the age-dependent loss of neuronal plasticity

The age-dependent loss of neuronal plasticity is a well-known phenomenon that is poorly understood. The loss of this capacity for axonal regeneration is emphasized following traumatic brain injury, which is a major cause of disability and death among adults in the US. We have previously shown the in...

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Autores principales: Thompson, Derick, Odufuwa, Abiodun E., Brissette, Catherine A., Watt, John A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10498476/
https://www.ncbi.nlm.nih.gov/pubmed/37711995
http://dx.doi.org/10.3389/fnagi.2023.1223273
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author Thompson, Derick
Odufuwa, Abiodun E.
Brissette, Catherine A.
Watt, John A.
author_facet Thompson, Derick
Odufuwa, Abiodun E.
Brissette, Catherine A.
Watt, John A.
author_sort Thompson, Derick
collection PubMed
description The age-dependent loss of neuronal plasticity is a well-known phenomenon that is poorly understood. The loss of this capacity for axonal regeneration is emphasized following traumatic brain injury, which is a major cause of disability and death among adults in the US. We have previously shown the intrinsic capacity of magnocellular neurons within the supraoptic nucleus to undergo axonal regeneration following unilateral axotomization in an age-dependent manner. The aim of this research was to determine the age-dependent molecular mechanisms that may underlie this phenomenon. As such, we characterized the transcriptome and DNA methylome of the supraoptic nucleus in uninjured 35-day old rats and 125-day old rats. Our data indicates the downregulation of a large number of axonogenesis related transcripts in 125-day old rats compared to 35-day old rats. Specifically, several semaphorin and ephrin genes were downregulated, as well as growth factors including FGF’s, insulin-like growth factors (IGFs), and brain-derived neurotrophic factor (BDNF). Differential methylation analysis indicates enrichment of biological processes involved in axonogenesis and axon guidance. Conversely, we observed a robust and specific upregulation of MHCI related transcripts. This may involve the activator protein 1 (AP-1) transcription factor complex as motif analysis of differentially methylated regions indicate enrichment of AP-1 binding sites in hypomethylated regions. Together, our data suggests a loss of pro-regenerative capabilities with age which would prevent axonal growth and appropriate innervation following injury.
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spelling pubmed-104984762023-09-14 Transcriptome and methylome of the supraoptic nucleus provides insights into the age-dependent loss of neuronal plasticity Thompson, Derick Odufuwa, Abiodun E. Brissette, Catherine A. Watt, John A. Front Aging Neurosci Neuroscience The age-dependent loss of neuronal plasticity is a well-known phenomenon that is poorly understood. The loss of this capacity for axonal regeneration is emphasized following traumatic brain injury, which is a major cause of disability and death among adults in the US. We have previously shown the intrinsic capacity of magnocellular neurons within the supraoptic nucleus to undergo axonal regeneration following unilateral axotomization in an age-dependent manner. The aim of this research was to determine the age-dependent molecular mechanisms that may underlie this phenomenon. As such, we characterized the transcriptome and DNA methylome of the supraoptic nucleus in uninjured 35-day old rats and 125-day old rats. Our data indicates the downregulation of a large number of axonogenesis related transcripts in 125-day old rats compared to 35-day old rats. Specifically, several semaphorin and ephrin genes were downregulated, as well as growth factors including FGF’s, insulin-like growth factors (IGFs), and brain-derived neurotrophic factor (BDNF). Differential methylation analysis indicates enrichment of biological processes involved in axonogenesis and axon guidance. Conversely, we observed a robust and specific upregulation of MHCI related transcripts. This may involve the activator protein 1 (AP-1) transcription factor complex as motif analysis of differentially methylated regions indicate enrichment of AP-1 binding sites in hypomethylated regions. Together, our data suggests a loss of pro-regenerative capabilities with age which would prevent axonal growth and appropriate innervation following injury. Frontiers Media S.A. 2023-08-30 /pmc/articles/PMC10498476/ /pubmed/37711995 http://dx.doi.org/10.3389/fnagi.2023.1223273 Text en Copyright © 2023 Thompson, Odufuwa, Brissette and Watt. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Thompson, Derick
Odufuwa, Abiodun E.
Brissette, Catherine A.
Watt, John A.
Transcriptome and methylome of the supraoptic nucleus provides insights into the age-dependent loss of neuronal plasticity
title Transcriptome and methylome of the supraoptic nucleus provides insights into the age-dependent loss of neuronal plasticity
title_full Transcriptome and methylome of the supraoptic nucleus provides insights into the age-dependent loss of neuronal plasticity
title_fullStr Transcriptome and methylome of the supraoptic nucleus provides insights into the age-dependent loss of neuronal plasticity
title_full_unstemmed Transcriptome and methylome of the supraoptic nucleus provides insights into the age-dependent loss of neuronal plasticity
title_short Transcriptome and methylome of the supraoptic nucleus provides insights into the age-dependent loss of neuronal plasticity
title_sort transcriptome and methylome of the supraoptic nucleus provides insights into the age-dependent loss of neuronal plasticity
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10498476/
https://www.ncbi.nlm.nih.gov/pubmed/37711995
http://dx.doi.org/10.3389/fnagi.2023.1223273
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