Structural changes in the dendritic spines and mitochondria of neurons in the brain are pointed out to involved in the pathogenesis/pathophysiology of schizophrenia and intellectual disability. Our research group proposed that mice deficient in protein called Schnurri-2 (Shn2) show symptoms of schizophrenia and intellectual disability. However, the change in intracellular structure like dendritic spines in Shn2 knockout (KO) mice is still unknown.

   In this study, three-dimensional morphological analysis of intracellular structure in brain hippocampal dentate gyrus cells of Shn2 KO mice was performed using a serial block surface scanning electron microscope (SBF-SEM). Immature dendritic morphology was observed in Shn2 KO mice, consisting of an increase in spine length and a decrease in diameter (Figure 1). There was also a significant reduction in nuclear volume and number of constricted mitochondria. In addition, the density of neurons increased in Shn2 KO mice. These results show that Shn2 KO mice can be used as a model to investigate the morphological abnormality of intracellular structures in schizophrenia, intellectual disorders and its related disorders.

　　　The present result clearly shows the relationship between schizophrenia and intellectual disability and structural changes of intracellular organs, and at the same time, it is expected to be applicable to early detection and treatment of such neurological diseases in the future.
 

Figure 1  3D reconstructions of dendrite gyrus in mouse brain by SBF-SEM. WT: wild type, Shn2 KO: Schnurri-2 KO mouse.

Collaborative Researchers

Akito Nakao, Koji Ohira, Tsuyoshi Miyakawa (Fujita Health University, Japan)
Naoyuki Miyazaki, Sachiko Yamada, Kazuyoshi Murata (NIPS)
 

Grants

The Grants-in-Aid for Scientific Research (A) and the Grant-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science and Technology, Japan, (KAKENHI)
Advanced Bioimaging Support (ABiS) from Grant-in-Aid for Scientific Research on Innovative Areas, Japan.