Blood expression levels of genes targeted by the stress hormones called glucocorticoids could be a physical measure, or biomarker, of risk for developing Post-Traumatic Stress Disorder (PTSD), according to a study conducted in rats by researchers at the Icahn School of Medicine at Mount Sinai and published August 11 in Proceedings of the National Academy of Sciences (PNAS). That also makes the steroid hormones’ receptor, the glucocorticoid receptor, a potential target for new drugs.
Post-Traumatic Stress Disorder (PTSD) is triggered by a terrifying event, either witnessed or experienced. Symptoms may include flashbacks, nightmares and severe anxiety, as well as uncontrollable thoughts about the event. Not everyone who experiences trauma develops PTSD, which is why the study aimed to identify biomarkers that could better measure each person’s vulnerability to the disorder.
“Our aim was to determine which genes are differentially expressed in relation to PTSD,” said lead investigator Rachel Yehuda, PhD, Professor of Psychiatry and Neuroscience and Director of the Traumatic Stress Studies Division at the Icahn School of Medicine at Mount Sinai. “We found that most of the genes and pathways that are different in PTSD-like animals compared to resilient animals are related to the glucocorticoid receptor, which suggests we might have identified a therapeutic target for treatment of PTSD,” said Dr. Yehuda, who also heads the Mental Health Patient Care Center and PTSD Research Program at the James J. Peters Veterans Affairs Medical Center in the Bronx.
The research team exposed a group of male and female rats to litter soiled by cat urine, a predatory scent that mimics a life-threatening situation. Most PTSD studies until now have used only male rats. Mount Sinai researchers included female rats in this study since women are more vulnerable than men to developing PTSD. The rats were then categorized based on their behavior one week after exposure to the scent. The authors also examined patterns of gene expression in the blood and in stress-responsive brain regions.
After one week of being exposed to soiled cat litter for 10 minutes, vulnerable rats exhibited higher anxiety and hyperarousal, and showed altered glucocorticoid receptor signaling in all tissues compared with resilient rats. Moreover, some rats were treated with a hormone that activates the glucocorticoid receptor called corticosterone one hour after exposure to the cat urine scent. These rats showed lower levels of anxiety and arousal one week later compared with untreated, trauma-exposed rats.
“PTSD is not just a disorder that affects the brain,” said co-investigator Nikolaos Daskalakis, MD, PhD, Associate Research Scientist in the Department of Psychiatry at the Icahn School of Medicine at Mount Sinai. “It involves the entire body, which is why identifying common regulators is key. The glucocorticoid receptor is the one common regulator that consistently stood out.”
Extreme close-ups of human eyes by Suren Manvelyan
Windows to the soul.
Research Aims to Create Versatile ‘Tapes’
Porphyrin molecules are essential to many biological processes, such as photosynthesis and respiration. Wilhelm Auwärter’s group is investigating these all-round talents at Technische Universität München. Normally, hydrogen attaches to the outer edges of the porphyrin core – named porphin, but other chemical entities can take the place of hydrogen, thereby changing the properties of the molecules.
Alissa Wiengarten, PhD student at the TUM Department of Physics, heats a porphin powder in a vacuum chamber. In the process, individual porphin molecules leave the collective and adhere to a silver surface, where they react with each other and assemble into small groups – all by themselves. Single molecules can desorb from the hot surface, while chains of two, three or more porphin units cannot. In this way the scientists were able to assemble chains of up to 90 porphin units.
Read more: http://www.laboratoryequipment.com/news/2014/08/research-aims-create-versatile-%E2%80%98tapes%E2%80%99
A team of researchers from the Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences have developed a new way of using electricity to open the blood-brain-barrier (BBB). The Vascular Enabled Integrated Nanosecond pulse (VEIN pulse) procedure consists of inserting…
New Blood: Tracing the Beginnings of Hematopoietic Stem Cells
Researchers uncover earliest clues yet to development of cells that produce all adult blood cells
Hematopoietic stem cells (HSCs) give rise to all other blood cell types, but their development and how their fate is determined has long remained a mystery. In a paper published online this week in Nature, researchers at the University of California, San Diego School of Medicine elaborate upon a crucial signaling pathway and the role of key proteins, which may help clear the way to generate HSCs from human pluripotent precursors, similar to advances with other kinds of tissue stem cells.
Principal investigator David Traver, PhD, professor in the Department of Cellular and Molecular Medicine, and colleagues focused on the Notch signaling pathway, a system found in all animals and known to be critical to the generation of HSCs in vertebrates. “Notch signaling between emitting and receiving cells is key to establishing HSC fate during development,” said Traver. “What has not been known is where, when and how Notch signal transduction is mediated.”
Traver and colleagues discovered that the Notch signal is transduced into HSC precursor cells from signal emitting cells in the somite – embryologic tissues that eventually contribute to development of major body structures, such as skeleton, muscle and connective tissues – much earlier in the process than previously anticipated.
More specifically, they found that JAM proteins, best known for helping maintain tight junctions between endothelial cells to prevent vascular leakage, were key mediators of Notch signaling. When the researchers caused loss of function in JAM proteins in a zebrafish model, Notch signaling and HSCs were also lost. When they enforced Notch signaling through other means, HSC development was rescued.
“To date, it has not been possible to generate HSCs de novo from human pluripotent precursors, like induced pluripotent stem cells,” said Traver. “This has been due in part to a lack of understanding of the complete set of factors that the embryo uses to make HSCs in vivo. It has also likely been due to not knowing in what order each required factor is needed.”
“Our studies demonstrate that Notch signaling is required much earlier than previously thought. In fact, it may be one of the earliest determinants of HSC fate. This finding strongly suggests that in vitro approaches to instruct HSC fate from induced pluripotent stem cells must focus on the Notch pathway at early time-points in the process. Our findings have also shown that JAM proteins serve as a sort of co-receptor for Notch signaling in that they are required to maintain close contact between signal-emitting and signal-receiving cells to permit strong activation of Notch in the precursors of HSCs.”
The findings may have far-reaching implications for eventual development of hematopoietic stem cell-based therapies for diseases like leukemia and congenital blood disorders. Currently, it is not possible to create HSCs from differentiation of embryonic stem cells or induced pluripotent stem cells – pluripotent cells artificially derived from non-pluripotent cells, such as skin cells – that are being used in other therapeutic research efforts.
Dangerous brain tumors hijack the brain’s existing blood supply throughout their progression, by growing only within narrow potential spaces between and along the brain’s thousands of small blood vessels, new research shows for the first time.
(Caption: This microscopic view of a mouse…
This particular moment in Star Trek is actually quite important. A lot of people don’t realise that understanding something is not the same as approving of something. This particular episode (A Taste of Armageddon) had a civilization where war was fought on computers instead of on the battlefield and instead of people dying in combat they would send the calculated amount of “casualities” into a camp to die. Kirk is outraged completely by this and rightly should be, but Spock is not so overtly disapproving. He understands why they might think their solution is better for their civilization and takes the time to think about why they are doing it. Even though he can understand why, he still believes it is wrong for them to be doing it.
There is a separation between understanding something and approving of something that a lot of people seem to miss.
— Carl Jung (via observando)