As reported in the latest issue of Bipolar Disorders, the journal of The International Society for Bipolar Disorders, levels of SP4 (specificity protein 4) were lower in two specific regions of the brain in postmortem samples from patients with bipolar disorder. The study suggests that normalization of SP4 levels could be a relevant pharmacological strategy for the treatment of mood disorders.
“We found that levels of SP4 protein in the brain’s prefrontal cortex and the cerebellum were lower in postmortem samples from patients with bipolar disorder, compared with samples from control subjects who did not have the disease,” said co-senior author Grace Gill, PhD, an associate professor in the department of anatomy and cellular biology at Tufts University School of Medicine and a member of the neuroscience; genetics; and cell, molecular and developmental biology program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts.
Gill’s laboratory team at Tufts collaborated with researchers from Spain and used postmortem samples from Spain’s University of the Basque Country brain collection program to examine SP4 protein levels in samples from 10 bipolar subjects and 10 control subjects matched for gender, age, and time since death.
The team focused on the prefrontal cortex and the cerebellum because brain imaging studies suggest that bipolar disorder is associated with changes in the structure of these brain regions. Little is known about the cellular and molecular changes that occur in bipolar disorder, especially in the cerebellum.
“Our findings suggest that reduced activity of the SP4 protein may be common in bipolar disorder,” stated co-senior author Belén Ramos, PhD, a former postdoctoral fellow in Gill’s lab and now a researcher at the Parc Sanitari Sant Joan de Déu (PSSJD) and the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) in Barcelona, Spain.
Ramos explained that SP4 belongs to a category of proteins known as transcription factors, which regulate gene expression. “While this study examined the SP4 protein levels, mutations in the gene encoding the SP4 protein have been associated with psychiatric diseases including bipolar disorder, a poorly understood disease characterized by episodes of abnormally elevated energy levels with or without depressive episodes, as well as schizophrenia, and major depressive disorder. Thus, our study adds to the growing body of evidence that alterations in gene regulation contribute to the development of psychiatric disorders,” said Ramos.
Further analysis showed that SP4 levels are regulated by neuronal activity, indicating that this transcription factor is important for normal neuronal signaling. “Looking at normal rat neurons in culture, we found that SP4 is rapidly degraded by enzymes in the absence of neuronal signaling, which we refer to as the non-depolarized state,” said first author Raquel Pinacho, BS, MS, a graduate student in Ramos’ lab in PSSJD.
In previous work, the researchers had identified an essential role for SP4 in regulating the structure of nerve cells during development. Taken together, the findings suggest that reduced levels of this protein may contribute to altered patterns of nerve cells in the brain.
“Moreover,” added Ramos, “we demonstrated that the destruction of SP4 by enzymes was inhibited by lithium, a drug widely used as a mood stabilizer for patients with bipolar disorder. When lithium was added to cells in the non-depolarized -- inactive -- state, levels of SP4 were stabilized and increased. This finding suggests that the therapeutic effects of lithium may be related, at least in part, to changes in gene expression leading to changes in cellular structure and function.”
In addition to measuring levels of SP4, Gill and colleagues assessed levels of SP1, a related transcription factor protein that has been reported to be altered in schizophrenia. Like SP4, SP1 was reduced in the cerebellum of subjects with bipolar disorder. According to the authors, this finding suggests that both factors may be relevant transcriptional regulators, low levels of which may contribute to the pathogenesis of bipolar disorder and other psychiatric diseases. However, unlike SP4, levels of SP1 did not appear to be regulated by neuronal activity, highlighting the complexity of the mechanisms involved in functional specificity in the SP transcription factor family.
Additional authors on the study are Nuria Villalmanzo, a research assistant in Ramos’s lab in PSSJD, Jasmin Lalonde, PhD, a postdoctoral fellow in Gill’s lab at TUSM; Josep Maria Haro, MD, PhD, of PSSJD and CIBERSAM; and J. Javier Meana, MD, PhD, professor in the department of pharmacology at the University of the Basque Country in Bizkaia, Spain, and CIBERSAM.
The study was funded by the National Institute of Child Health and Human Development, part of the National Institutes of Health, a Marie Curie International Reintegration Grant (European Union) and the Plan National de Investigación (Spain). This study was also supported by fellowships to authors from the Spanish Ministry of Science and Education/Fulbright, CIBERSAM, and from the Canadian Institutes of Health Research.
Pinacho R, Villalmanzo N, Lalonde J, Haro JM, Meana JJ, Gill G, Ramos B. Bipolar Disorders. “The transcription factor SP4 is reduced in postmortem cerebellum of bipolar disorder subjects: control by depolarization and lithium.” Published online October 21, 2011, doi: 10.1111/j.1399-5618.2011.00941.xAbout Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences
Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University are international leaders in innovative medical education and advanced research. The School of Medicine and the Sackler School are renowned for excellence in education in general medicine, biomedical sciences, special combined degree programs in business, health management, public health, bioengineering and international relations, as well as basic and clinical research at the cellular and molecular level. Ranked among the top in the nation, the School of Medicine is affiliated with six major teaching hospitals and more than 30 health care facilities. Tufts University School of Medicine and the Sackler School undertake research that is consistently rated among the highest in the nation for its effect on the advancement of medical science.
If you are a member of the media interested in learning more about this topic, or speaking with a faculty member at the Tufts University School of Medicine, the Sackler School of Graduate Biomedical Sciences, or another Tufts health sciences researcher, please contact Siobhan Gallagher at 617-636-6586.
Siobhan Gallagher | Newswise Science News
Further reports about: > Biomedical > Biomedical Science > Medicine > SP4 > Sackler > Spain > Tufts > bipolar > bipolar disorder > frontal cortex > health services > medical science > mood disorder > nerve cell > neuronal activity > prefrontal cortex > protein levels > psychiatric disease > psychiatric disorder > transcription factor
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy