J Psychiatry Neurosci 2015;40(2):78-88
Seong-Wook Kim, MS*; Misun Seo, MS*; Duk-Soo Kim, PhD; Moonkyung Kang, MS; Yeon-Soo Kim, PhD; Hae-Young Koh, PhD; Hee-Sup Shin, MD, PhD
Background: Decreased expression of phospholipase C-β1 (PLC-β1) has been observed in the brains of patients with schizophrenia, but, to our knowledge, no studies have shown a possible association between this altered PLC-β1 expression and the pathogenesis of schizophrenia. Although PLC-β1-null (PLC-β1−/−) mice exhibit multiple endophenotypes of schizophrenia, it remains unclear how regional decreases in PLC-β1 expression in the brain contribute to specific behavioural defects.
Methods: We selectively knocked down PLC-β1 in the medial prefrontal cortex (mPFC) using a small hairpin RNA strategy in mice.
Results: Silencing PLC-β1 in the mPFC resulted in working memory deficits, as assayed using the delayed non-match-to-sample T-maze task. Notably, however, other schizophrenia-related behaviours observed in PLC-β1−/− mice, including phenotypes related to locomotor activity, sociability and sensorimotor gating, were normal in PLC-β1 knockdown mice.
Limitations: Phenotypes of PLC-β1 knockdown mice, such as locomotion, anxiety and sensorimotor gating, have already been published in our previous studies. Further, the neural mechanisms underlying the working memory deficit in mice may be different from those in human schizophrenia.
Conclusion: These results indicate that PLC-β1 signalling in the mPFC is required for working memory. Importantly, these results support the notion that the decrease in PLC-β1 expression in the brains of patients with schizophrenia is a pathogenically relevant molecular marker of the disorder.
*These authors contributed equally to this work.
Submitted Dec. 16, 2013; Revised Mar. 16, Apr. 11, May 16, 2014; Accepted June 2, 2014; Early-released Sept. 30, 2014.
Acknowledgements: We thank Dr. Taesup Cho and Dr. Sukchan Lee for his help in the preparation of the manuscripts. This work was supported by IBS-R001-D1, and the 21C Frontier Proteomics Program of the Ministry of Education, Sciecne and Technology, Korea.
Affiliations: From the Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon, Korea (S.-K. Kim, Shin); Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Korea (Seo, Koh); Department of Neuroscience, Korea University of Science and Technology, Daejeon, Korea (S.-W. Kim, Seo, Koh, Shin); Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si, Korea (D.-S. Kim); Indang Institute of Molecular Biology, Inje University, Seoul, Korea (Kang, Y.-S. Kim); Department of Smart Foods and Drugs, Inje University, Seoul, Korea (Y.-S. Kim).
Competing interests: None declared.
Contributors: S.-W. Kim, M. Seo and H.-S. Shin designed the study. S.-W. Kim, M. Seo, D.-S. Kim, M. Kang and Y.-S. Kim acquired the data, which S.-W. Kim, M. Seo, D.-S. Kim and H.-Y. Koh analyzed. H.-Y. Koh and H.-S. Shin reviewed the article, which all authors wrote and approved for publication.
Correspondence to: H.-S. Shin, Center for Cognition and Sociality, Institute for Basic Science (IBS), 70 Yuseong-daero 1689-gil, Yusung-gu, Daejeon 305-811, Republic of Korea; firstname.lastname@example.org