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Mol Neurobiol. 2017 Nov;54(9):7353-7368. doi: 10.1007/s12035-016-0207-6. Epub 2016 Nov 5.

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

Author information

1
SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, South Korea.
2
Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
3
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, South Korea.
4
KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, South Korea.
5
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
6
College of Pharmacy, Inje University, Gimhae, 621-749, South Korea.
7
Department of Psychiatry and Program in Neuroscience, McLean Hospital, Harvard Medical School, Belmont, MA, 02478, USA.
8
Department of Life Sciences, Ewha Womans University, Seoul, 120-750, South Korea.
9
SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, South Korea. qwonkim@snu.ac.kr.
10
Crop Biotechnology Institute, GreenBio Science and Technology, Seoul National University, Pyeongchang, 25354, South Korea. qwonkim@snu.ac.kr.

Abstract

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.

KEYWORDS:

Anxiety-like behavior; Fluoxetine; Glutamate receptors; Ninj1; OCD; Repetitive behavior

PMID:
27815839
DOI:
10.1007/s12035-016-0207-6
[Indexed for MEDLINE]

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