Disruption of Ninjurin1 Leads to Repetitive and Anxiety-Like Behaviors in Mice

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Over the last few decades, molecular neurobiology has uncovered many genes whose deficiency in mice results in behavioral traits associated with human neuropsychiatric disorders such as autism, obsessive-compulsive disorder (OCD), and schizophrenia. However, the etiology of these common diseases remains enigmatic with the potential involvement of a battery of genes. Here, we report abnormal behavioral phenotypes of mice deficient in a cell adhesion molecule Ninjurin 1 (Ninj1), which are relevant to repetitive and anxiety behaviors of neuropsychiatric disorders. Ninj1 knockout (KO) mice exhibit compulsive grooming-induced hair loss and self-made lesions as well as increased anxiety-like behaviors. Histological analysis reveals that Ninj1 is predominantly expressed in cortico-thalamic circuits, and neuron-specific Ninj1 conditional KO mice manifest aberrant phenotypes similar to the global Ninj1 KO mice. Notably, the brains of Ninj1 KO mice display altered synaptic transmission in thalamic neurons as well as a reduced number of functional synapses. Moreover, the disruption of Ninj1 leads to glutamatergic abnormalities, including increased ionotropic glutamate receptors but reduced glutamate levels. Furthermore, chronic treatment with fluoxetine, a drug reportedly ameliorates compulsive behaviors in mice, prevents progression of hair loss and alleviates the compulsive grooming and anxiety-like behavior of Ninj1 KO mice. Collectively, our results suggest that Ninj1 could be involved in neuropsychiatric disorders associated with impairments of repetitive and anxiety behaviors.
Publisher
HUMANA PRESS INC
Issue Date
2017-11
Language
English
Article Type
Article
Keywords

OBSESSIVE-COMPULSIVE DISORDER; AUTISTIC-LIKE BEHAVIORS; CENTRAL-NERVOUS-SYSTEM; NEUROPSYCHIATRIC DISORDERS; SPECTRUM DISORDERS; ADHESION MOLECULE; RECEPTOR FUNCTION; MUTANT MICE; DYSFUNCTION; NEUROBIOLOGY

Citation

MOLECULAR NEUROBIOLOGY, v.54, no.9, pp.7353 - 7368

ISSN
0893-7648
DOI
10.1007/s12035-016-0207-6
URI
http://hdl.handle.net/10203/226699
Appears in Collection
BS-Journal Papers(저널논문)
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