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
Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care
Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
17.11.2017 | Physics and Astronomy
17.11.2017 | Health and Medicine
17.11.2017 | Studies and Analyses