Inducible nitric oxide synthase (NOS2) knockout mice as a model of trichotillomania

PeerJ

article

Plinio C. Casarotto¹  Caroline Biojone¹  Karina Montezuma³  Fernando Q. Cunha²  Samia R.L. Joca³  Eero Castren¹  Francisco S. Guimaraes² 

[1]Neuroscience Center, University of Helsinki

[2]Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo

[3]Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo

[4]NAPNA: Center for Interdisciplinary Research on Applied Neurosciences, University of São Paulo

关键词: Trichotillomania;    Barbering;    NOS2;    Memantine;    Clomipramine;   

DOI  :  10.7717/peerj.4635

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundTrichotillomania (TTM) is an impulse control disorder characterized by repetitive hair pulling/trimming. Barbering behavior (BB) observed in laboratory animals is proposed as a model of TTM. The neurobiological basis of TTM is unclear, but involves striatal hyperactivity and hypoactivation of the prefrontal cortex.MethodsIn this study, we evaluated the BB in knockout mice for the inducible isoform of nitric oxide synthase (NOS2KO) and the consequences of silencing this enzyme in PC12 cell differentiation.ResultsNOS2KO exhibit exacerbated BB, starting four weeks of age, and increased repetitive movements compared to wild-type mice (WT). The expression of BB was attenuated by repeated treatment with clomipramine, a clinically approved drug to treat TTM in humans, or memantine, an antagonist of NMDA receptors, as well as partial rescue of NOS2 expression in haploinsufficient animals. The silencing of NOS2 expression reduced the MAP2 (microtubule-associated protein 2) levels in activity-induced differentiated PC12 cells.DiscussionOur data led us to propose that NOS2 is putatively involved in the neuronal maturation of the inhibitory afferent pathways during neurodevelopment, and such inadequate inhibition of motor programs might be associated to the observed phenotype.

【 授权许可】

CC BY