Increased 5-HT2C receptor editing predisposes to PTSD-like behaviors and alters BDNF and cytokines signaling

Translational Psychiatry
Mathilde RègueR Mongeau

Abstract

Post-traumatic stress disorder (PTSD) is a trauma- and stress-related disorder with dysregulated fear responses and neurobiological impairments, notably at neurotrophic and inflammation levels. Understanding the mechanisms underlying this disease is crucial to develop PTSD models that meet behavioral and neurobiological validity criteria as well as innovative therapeutic approaches. Serotonin 2C receptors (5-HT2CR) are known for their important role in anxiety, and mice having only the fully edited VGV isoform of 5-HT2CR, which thereby overexpressed brain 5-HT2CR, are of special interest to study PTSD predisposition. Innate and conditioned fear-related behaviors were assessed in VGV and wild-type mice. mRNA expression of brain-derived neurotrophic factor (BDNF), tissue-plasminogen activator (tPA), and pro-inflammatory cytokines (IL-6, IL-1β, and calcineurin) were measured by qRT-PCR. The effect of acute and chronic paroxetine was evaluated on both behavior and gene expression. VGV mice displayed greater fear expression, extensive fear extinction deficits, and fear generalization. Paroxetine restored fear extinction in VGV mice when administered acutely and decreased innate fear and fear generalization when administered chronica...Continue Reading

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Citations

Jun 28, 2019·Frontiers in Behavioral Neuroscience·Graziano Pinna
Aug 6, 2020·Genes·Alessandro Barbon, Chiara Magri
Jul 28, 2020·Frontiers in Pharmacology·Giuseppe Di GiovanniPhilippe De Deurwaerdère
Apr 21, 2021·The European Journal of Neuroscience·Ellen DoneyCaroline Menard
Jul 15, 2021·Neurobiology of Stress·Shuming AnXiaohua Cao

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Methods Mentioned

BETA
PCR

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