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Kynurenic acid accumulation underlies learning and memory impairment associated with aging

A general feature of animal aging is decline in learning and memory. Here we show that in Caenorhabditis elegans, a significant portion of this decline is due to accumulation of kynurenic acid (KYNA), an endogenous antagonist of neural N-methyl-D-aspartate receptors (NMDARs). We show that activation...

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Detalles Bibliográficos
Autores principales: Vohra, Mihir, Lemieux, George A., Lin, Lin, Ashrafi, Kaveh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828390/
https://www.ncbi.nlm.nih.gov/pubmed/29386332
http://dx.doi.org/10.1101/gad.307918.117
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author Vohra, Mihir
Lemieux, George A.
Lin, Lin
Ashrafi, Kaveh
author_facet Vohra, Mihir
Lemieux, George A.
Lin, Lin
Ashrafi, Kaveh
author_sort Vohra, Mihir
collection PubMed
description A general feature of animal aging is decline in learning and memory. Here we show that in Caenorhabditis elegans, a significant portion of this decline is due to accumulation of kynurenic acid (KYNA), an endogenous antagonist of neural N-methyl-D-aspartate receptors (NMDARs). We show that activation of a specific pair of interneurons either through genetic means or by depletion of KYNA significantly improves learning capacity in aged animals even when the intervention is applied in aging animals. KYNA depletion also improves memory. We show that insulin signaling is one factor in KYNA accumulation.
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spelling pubmed-58283902018-07-01 Kynurenic acid accumulation underlies learning and memory impairment associated with aging Vohra, Mihir Lemieux, George A. Lin, Lin Ashrafi, Kaveh Genes Dev Research Communication A general feature of animal aging is decline in learning and memory. Here we show that in Caenorhabditis elegans, a significant portion of this decline is due to accumulation of kynurenic acid (KYNA), an endogenous antagonist of neural N-methyl-D-aspartate receptors (NMDARs). We show that activation of a specific pair of interneurons either through genetic means or by depletion of KYNA significantly improves learning capacity in aged animals even when the intervention is applied in aging animals. KYNA depletion also improves memory. We show that insulin signaling is one factor in KYNA accumulation. Cold Spring Harbor Laboratory Press 2018-01-01 /pmc/articles/PMC5828390/ /pubmed/29386332 http://dx.doi.org/10.1101/gad.307918.117 Text en © 2018 Vohra et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Communication
Vohra, Mihir
Lemieux, George A.
Lin, Lin
Ashrafi, Kaveh
Kynurenic acid accumulation underlies learning and memory impairment associated with aging
title Kynurenic acid accumulation underlies learning and memory impairment associated with aging
title_full Kynurenic acid accumulation underlies learning and memory impairment associated with aging
title_fullStr Kynurenic acid accumulation underlies learning and memory impairment associated with aging
title_full_unstemmed Kynurenic acid accumulation underlies learning and memory impairment associated with aging
title_short Kynurenic acid accumulation underlies learning and memory impairment associated with aging
title_sort kynurenic acid accumulation underlies learning and memory impairment associated with aging
topic Research Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828390/
https://www.ncbi.nlm.nih.gov/pubmed/29386332
http://dx.doi.org/10.1101/gad.307918.117
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