Summary: A cell membrane protein that regulates neuroplasticity regulates the function of a gene associated with schizophrenia, a new study reports.
Source: American Physiological Society.
Mice lacking protein show signs of mental illness.
Researchers from the University of California, San Diego, have identified a protein that regulates a gene associated with schizophrenia. The study is published in the Journal of Neurophysiology.
Schizophrenia—a chronic mental illness that affects a person’s thoughts, feelings and behavior—is determined in part by genetic makeup. The DISC1 gene is associated with developing schizophrenia. DISC1 is involved in the growth of nerve cells, proper nerve signaling and the ability of the brain to grow and adjust (neuroplasticity) throughout a person’s lifetime. Loss of DISC1 function can interrupt the normal signaling pattern, which may lead to schizophrenia-like symptoms, such as movement disorders, memory problems and reduced expression of emotions.
Caveolin (Cav-1) is a cell membrane protein that promotes nerve signaling and neuroplasticity in the nervous system. In this study, the research team looked at the interaction between Cav-1 and DISC1 in the nerve cells of mice. The team is the first to find that Cav-1 regulates the function of DISC1.
Mice that did not express the Cav-1 protein had less DISC1 expression in the brain and showed symptoms on the molecular level similar to that seen in brains afflicted with schizophrenia. When the researchers reintroduced Cav-1 specifically in nerve cells of these mice, DISC1 protein, in addition to proteins critical for synaptic plasticity (the ability of neurons to grow and form new connections), returned to normal levels.
The study’s findings have significant implications for schizophrenia treatment. “While pharmacological treatments such as antipsychotics are available for schizophrenia, these classes of drugs show poor efficacy for most patients, especially in reversing cognitive abnormalities,” wrote the researchers. “Further understanding of how Cav-1 modulates DISC1 to maintain and organize neuronal growth signaling and proper function is of upmost importance to better understand and identify potential molecular targets for treating schizophrenia.”
About this genetics research article
Source: Stacy Brooks – American Physiological Society Image Source: NeuroscienceNews.com image is in the public domain. Original Research:Abstract for “Caveolin-1 Regulation of Disrupted-in-Schizophrenia-1 as a Potential Therapeutic Target for Schizophrenia” by Adam Kassan, Junji Egawa, Zheng Zhang, Angels Almenar-Queralt, Quynh My Nguyen, Yasaman Lajevardi, Kaitlyn Kim, Edmund Posadas, Dilip V Jeste, David M Roth, Piyush M Patel, Hemal H Patel, and Brian P Head in Journal of Neurophysiology. Published online November 2 2016 doi:10.1152/jn.00481.2016
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[cbtabs][cbtab title=”MLA”]American Physiological Society “Nerve-Signaling Protein Regulates Gene Associated with Schizophrenia.” NeuroscienceNews. NeuroscienceNews, 60 January 2017. <https://neurosciencenews.com/genetics-schizophrenia-protein-5879/>.[/cbtab][cbtab title=”APA”]American Physiological Society (2017, January 60). Nerve-Signaling Protein Regulates Gene Associated with Schizophrenia. NeuroscienceNew. Retrieved January 60, 2017 from https://neurosciencenews.com/genetics-schizophrenia-protein-5879/[/cbtab][cbtab title=”Chicago”]American Physiological Society “Nerve-Signaling Protein Regulates Gene Associated with Schizophrenia.” https://neurosciencenews.com/genetics-schizophrenia-protein-5879/ (accessed January 60, 2017).[/cbtab][/cbtabs]
Caveolin-1 Regulation of Disrupted-in-Schizophrenia-1 as a Potential Therapeutic Target for Schizophrenia
Background: Schizophrenia is a debilitating psychiatric disorder manifested in early adulthood. Disrupted-In-Schizophrenia-1 (DISC1) is a susceptible gene for schizophrenia (54, 76, 101) implicated in neuronal development, brain maturation and neuroplasticity (12, 20). Therefore, DISC1 is a promising candidate gene for schizophrenia, but the molecular mechanisms underlying its role in the pathogenesis of the disease are still poorly understood. Interestingly, Caveolin-1 (Cav-1), a cholesterol binding and scaffolding protein, regulates neuronal signal transduction and promotes neuroplasticity. Here we examined the role of Cav-1 in mediating DISC1 expression in neurons in vitro and the hippocampus in vivo.
Methods and Results: Overexpressing Cav-1 specifically in neurons using a neuron specific synapsin promoter (SynCav1) increased expression of DISC1 and proteins involved in synaptic plasticity (PSD95, synaptobrevin, synaptophysin, neurexin, and syntaxin-1). Similarly, SynCav1-transfected differentiated human neurons derived from induced pluripotent stem cells (hiPSCs) exhibited increased expression of DISC1 and markers of synaptic plasticity. Conversely, hippocampi from Cav-1 knockout (KO) exhibited decreased expression of DISC1 and proteins involved in synaptic plasticity. Finally, SynCav1 delivery to the hippocampus of Cav-1 KO mice and Cav-1 KO neurons in culture restored expression of DISC1 and markers of synaptic plasticity. Furthermore, we found that Cav-1 co-immunoprecipitated with DISC1 in brain tissues.
Conclusion: These findings suggest an important role by which neuronal Cav-1 regulates DISC1 neurobiology with implications for synaptic plasticity. Therefore, SynCav1 might be a potential therapeutic target for restoring neuronal function in schizophrenia.
“Caveolin-1 Regulation of Disrupted-in-Schizophrenia-1 as a Potential Therapeutic Target for Schizophrenia” by Adam Kassan, Junji Egawa, Zheng Zhang, Angels Almenar-Queralt, Quynh My Nguyen, Yasaman Lajevardi, Kaitlyn Kim, Edmund Posadas, Dilip V Jeste, David M Roth, Piyush M Patel, Hemal H Patel, and Brian P Head in Journal of Neurophysiology. Published online November 2 2016 doi:10.1152/jn.00481.2016