King's College London

TY - JOUR

T1 - Negative evidence for a functional role of neuronal DNMT3a in persistent pain

AU - Saunders, Jessica

AU - Hore, Zoe

AU - Gentry, Clive

AU - McMahon, Stephen

AU - Denk, Franziska

PY - 2018/9/12

Y1 - 2018/9/12

N2 - Traditionally, neuroscience has had to rely on mixed tissue analysis to examinetranscriptional and epigenetic changes in the context of nervous system function orpathology. However, particularly when studying chronic pain conditions, this approachcan be flawed, since it neglects to take into account the shifting contribution of differentcell types across experimental conditions. Here, we demonstrate this using the exampleof DNA methyltransferases (DNMTs) – a group of epigenetic modifiers consisting ofDnmt1, Dnmt3a, and Dnmt3b in mammalian cells. We used sensory neuron-specificknockout mice for Dnmt3a/3b as well as pharmacological blockade of Dnmt1 to studytheir role in nociception. In contrast to previous analyses on whole tissue, we find thatDnmt3a and 3b protein is not expressed in adult DRG neurons, that none of the DNAmethyltransferases are regulated with injury and that interfering with their function has noeffect on nociception. Our results therefore currently do not support a role for neuronalDNA methyltransferases in pain processing in adult animals.

AB - Traditionally, neuroscience has had to rely on mixed tissue analysis to examinetranscriptional and epigenetic changes in the context of nervous system function orpathology. However, particularly when studying chronic pain conditions, this approachcan be flawed, since it neglects to take into account the shifting contribution of differentcell types across experimental conditions. Here, we demonstrate this using the exampleof DNA methyltransferases (DNMTs) – a group of epigenetic modifiers consisting ofDnmt1, Dnmt3a, and Dnmt3b in mammalian cells. We used sensory neuron-specificknockout mice for Dnmt3a/3b as well as pharmacological blockade of Dnmt1 to studytheir role in nociception. In contrast to previous analyses on whole tissue, we find thatDnmt3a and 3b protein is not expressed in adult DRG neurons, that none of the DNAmethyltransferases are regulated with injury and that interfering with their function has noeffect on nociception. Our results therefore currently do not support a role for neuronalDNA methyltransferases in pain processing in adult animals.

UR - http://www.scopus.com/inward/record.url?scp=85054825632&partnerID=8YFLogxK

U2 - 10.3389/fnmol.2018.00332

DO - 10.3389/fnmol.2018.00332

M3 - Article

VL - 11

JO - Frontiers in Molecular Neuroscience

JF - Frontiers in Molecular Neuroscience

SN - 1662-5099

M1 - 332

ER -