Spatial Learning Is Associated with Antagonist Outcomes for DNA Methylation and DNA Hydroxymethylation in the Transcriptional Regulation of the Ryanodine Receptor 3

Increasing attention has been drawn to the role that intracellular calcium stores play in neuronal function. Ryr3 is an intracellular calcium channel that contributes to hippocampal long-term potentiation, dendritic spine function, and higher cognitive processes. Interestingly, stimuli that increase...

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Main Authors: Rodrigo F. Torres, Bredford Kerr
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2021/9930962
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author Rodrigo F. Torres
Bredford Kerr
author_facet Rodrigo F. Torres
Bredford Kerr
author_sort Rodrigo F. Torres
collection DOAJ
description Increasing attention has been drawn to the role that intracellular calcium stores play in neuronal function. Ryr3 is an intracellular calcium channel that contributes to hippocampal long-term potentiation, dendritic spine function, and higher cognitive processes. Interestingly, stimuli that increase neuronal activity upregulate the transcriptional activity of Ryr3 and augment DNA methylation in its proximal promoter. However, if these observations are valid for complex behavioral tasks such as learning and memory remains being evaluated. Relative expression analysis revealed that spatial learning increased the hippocampal levels of Ryr3, whereas mice trained using a visible platform that resulted in no spatial association showed reduced expression. Interestingly, we also observed that specific DNA modifications accompanied these opposite transcriptional changes. Increased DNA methylation was observed in hippocampal samples from spatially trained mice, and increased DNA hydroxymethylation was found in samples from mice trained using a visible platform. Both DNA modifications were not altered in control regions, suggesting that these changes are not generalized, but rather specific modifications associated with this calcium channel’s transcriptional regulation. Our two experimental groups underwent the same physical task differing only in the spatial learning component, highlighting the tight relationship between DNA modifications and transcriptional activity in a relevant context such as behavioral training. Our results complement previous observations and suggest that DNA modifications are a reliable signal for the transcriptional activity of Ryr3 and can be useful to understand how conditions such as aging and neuropathological diseases determine altered Ryr3 expression.
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spelling doaj-art-9f0a1a8d5f954f39b6822894c958090a2025-02-03T01:08:48ZengWileyNeural Plasticity2090-59041687-54432021-01-01202110.1155/2021/99309629930962Spatial Learning Is Associated with Antagonist Outcomes for DNA Methylation and DNA Hydroxymethylation in the Transcriptional Regulation of the Ryanodine Receptor 3Rodrigo F. Torres0Bredford Kerr1Departamento de Ciencias Básicas, Facultad de Medicina, Universidad Católica de la Santísima Concepción, Concepción 4090541, ChileCentro de Biología Celular y Biomedicina-CEBICEM, Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago 7510157, ChileIncreasing attention has been drawn to the role that intracellular calcium stores play in neuronal function. Ryr3 is an intracellular calcium channel that contributes to hippocampal long-term potentiation, dendritic spine function, and higher cognitive processes. Interestingly, stimuli that increase neuronal activity upregulate the transcriptional activity of Ryr3 and augment DNA methylation in its proximal promoter. However, if these observations are valid for complex behavioral tasks such as learning and memory remains being evaluated. Relative expression analysis revealed that spatial learning increased the hippocampal levels of Ryr3, whereas mice trained using a visible platform that resulted in no spatial association showed reduced expression. Interestingly, we also observed that specific DNA modifications accompanied these opposite transcriptional changes. Increased DNA methylation was observed in hippocampal samples from spatially trained mice, and increased DNA hydroxymethylation was found in samples from mice trained using a visible platform. Both DNA modifications were not altered in control regions, suggesting that these changes are not generalized, but rather specific modifications associated with this calcium channel’s transcriptional regulation. Our two experimental groups underwent the same physical task differing only in the spatial learning component, highlighting the tight relationship between DNA modifications and transcriptional activity in a relevant context such as behavioral training. Our results complement previous observations and suggest that DNA modifications are a reliable signal for the transcriptional activity of Ryr3 and can be useful to understand how conditions such as aging and neuropathological diseases determine altered Ryr3 expression.http://dx.doi.org/10.1155/2021/9930962
spellingShingle Rodrigo F. Torres
Bredford Kerr
Spatial Learning Is Associated with Antagonist Outcomes for DNA Methylation and DNA Hydroxymethylation in the Transcriptional Regulation of the Ryanodine Receptor 3
Neural Plasticity
title Spatial Learning Is Associated with Antagonist Outcomes for DNA Methylation and DNA Hydroxymethylation in the Transcriptional Regulation of the Ryanodine Receptor 3
title_full Spatial Learning Is Associated with Antagonist Outcomes for DNA Methylation and DNA Hydroxymethylation in the Transcriptional Regulation of the Ryanodine Receptor 3
title_fullStr Spatial Learning Is Associated with Antagonist Outcomes for DNA Methylation and DNA Hydroxymethylation in the Transcriptional Regulation of the Ryanodine Receptor 3
title_full_unstemmed Spatial Learning Is Associated with Antagonist Outcomes for DNA Methylation and DNA Hydroxymethylation in the Transcriptional Regulation of the Ryanodine Receptor 3
title_short Spatial Learning Is Associated with Antagonist Outcomes for DNA Methylation and DNA Hydroxymethylation in the Transcriptional Regulation of the Ryanodine Receptor 3
title_sort spatial learning is associated with antagonist outcomes for dna methylation and dna hydroxymethylation in the transcriptional regulation of the ryanodine receptor 3
url http://dx.doi.org/10.1155/2021/9930962
work_keys_str_mv AT rodrigoftorres spatiallearningisassociatedwithantagonistoutcomesfordnamethylationanddnahydroxymethylationinthetranscriptionalregulationoftheryanodinereceptor3
AT bredfordkerr spatiallearningisassociatedwithantagonistoutcomesfordnamethylationanddnahydroxymethylationinthetranscriptionalregulationoftheryanodinereceptor3