Disruption of Ninjurin1 Causes Obsessive-Compulsive Disorder-like Behaviors in Mice
Ninjurin1 결손 마우스에서 강박 장애 유사증상 발현에 관한 연구
- Le Hoang
- Kyu-Won Kim
- 약학대학 약학과
- Issue Date
- 서울대학교 대학원
- Ninjurin1; obsessive-compulsive disorder; OCD-like behaviors; anxiety-like behaviors; fluoxetine; glutamate signaling
- 학위논문 (박사)-- 서울대학교 대학원 : 약학과 의약생명과학전공, 2017. 2. 김규원.
- Obsessive-compulsive disorder (OCD) is a common psychiatric disorder that affects approximately 2 % of the global population and is characterized by the presence of intrusive and distressing thoughts (obsessions) and/or repetitive behaviors (compulsions). Over the last few decades, molecular neurobiology has uncovered several genes whose deficiency in mice results in behavioral traits associated with human OCD. However, the mechanisms that underlie OCD remain largely unknown. Here I show the relationship between OCD and Ninjurin 1 (Ninj1), a small cell adhesion molecule that is known to play various roles in nerve regeneration and inflammation. Ninj1 knockout (KO) mice exhibit compulsive grooming-induced hair loss and self-made lesions as well as increased anxiety-like behaviors that are responsive to fluoxetine, a first-line OCD treatment. Ninj1 is highly expressed in cortico-thalamic circuits, which are critical areas that are implicated in OCD. 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. Intriguingly, Ninj1 KO brains display reduced numbers of functional synapses and impaired neuronal branching, which results in altered neurotransmission in thalamic circuits. Moreover, the disruption of Ninj1 leads to abnormalities in glutamate signaling, which reflects the function of Ninj1 as a regulator of N-methyl-D-aspartate (NMDA)-type glutamate receptor stability. Collectively, my results demonstrate that Ninj1 deficiency in mice causes OCD-like behaviors and that Ninj1 could be a new genetic component of human OCD.