TY - JOUR
AR - NNB-2021-1-102
TI - DNA Methyltransferase Inhibitor Successfully Treats Obsessive-Compulsive Disorder in Various Mouse Models
AU - German, Todorov
AU - David, Ashurov
AU - Catarina, Cunha
JO - Neurology and Neurobiology
PY - 2021
DA - Wed 31, Mar 2021
SN - 2613-7828
DO - http://dx.doi.org/10.31487/j.NNB.2021.01.02
UR - https://www.sciencerepository.org/dna-methyltransferase-inhibitor-successfully-treats-obsessive-compulsive-disorder_NNB-2021-1-102 
KW - Epigenetics, obsessive-compulsive disorder, synaptic plasticity, cancer drugs, optogenetics
AB - Mental health disorders are manifested in families yet cannot be fully explained by classical Mendelian genetics. Changes in gene expression via epigenetics present a plausible mechanism. Anxiety often leads to avoidant behaviours, which upon repetition may become habitual, maladaptive, and resistant to extinction as observed in obsessive-compulsive disorders (OCD). Psychophysical models of OCD propose that anxiety (amygdala) and habits (dorsolateral striatum, DLS) may be causally linked. The amygdala activates spiny projection neurons in the DLS. Repetitive amygdala terminal stimulation in the DLS elicits long-term OCD-like behaviour in mice associated with circuitry changes and gene methylation-mediated decrease in protein phosphatase 1 (PP1). Treatment of OCD-like grooming behaviour in Slitrk5, SAPAP3, and laser-stimulated mice with one dose of RG108 (DNA methyltransferase inhibitor), leads to marked symptom improvement lasting for at least one week as well as a complete reversal of abnormal changes in the circuitry and PP1 activity.