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Archive - Jan 29, 2015

Novel Study of Dopamine-Releasing Neurons in Forebrain May Impact Understanding of Schizophrenia, Parkinson’s, and Many Diseases Involving Movement Disorder

Scientists studying hatchling zebrafish fish have made a new advance in in understanding the brain chemical dopamine that influences movement. The team from the University of Leicester (UK) Department of Biology has examined the transparent hatchling zebrafish to gain new insights into the working of neurons in areas of the brain that are normally difficult to access. As a result, they have discovered, for the first time, both when and why the particular cells in the brain that affect movement are active. The new study was published recently online in an open-access article in Current Biology and will appear the February 2015 print issue of Current Biology. Senior author Dr. Jonathan McDearmid said, “Our research is aimed at understanding how dopamine, a neurochemical secreted by nerve cells (neurons) in the brain, influences neuronal networks in the spinal cord that control motor behaviour. “Our understanding of dopamine function is largely derived from the study of dopamine-releasing neurons that are located within the midbrain, a structure located near to the base of the brain. However, vertebrates, including humans, also possess a cluster of dopamine-containing neurons in the forebrain. Unlike their midbrain counterparts, these neurons extend projections to the spinal cord, a region that is dedicated to the production of motor behaviors (such as walking and swimming). We know relatively little about the role this forebrain population plays in regulating behaviour: the main aim of our study was to address this problem.” The Leicester team was able to overcome this problem by examining hatchling zebrafish which are transparent and lack bone tissue, which makes the brain accessible to study.

Young Scientist Wins Prestigious Friedrich Miescher Prize for Work on Cas9 “Genetic Scissors” Tool

Martin Jinek, Ph.D., a professor in the Department of Biochemistry at the University of Zurich has won the Friedrich Miescher Prize, which carries 20,000 Swiss francs (CHF) in prize money,according to a January 29, 2015 press release from the University of Zurich. The award is the highest accolade for budding researchers in biochemistry in Switzerland. The Swiss Society for Molecular and Cellular Biosciences has awarded this year’s Friedrich Miescher Prize to 35-year-old Dr. Jinek in recognition of his work on the microbial defense system and the genetic engineering tool CRISPR-Cas9. The biochemist from the Czech Republic helped make the protein Cas9 an essential tool in genetic engineering. The molecule serves as a versatile pair of scissors to process the genetic material of animal or plant cells. Cas9 can be used to cut out, add, activate, or suppress genes as and when required. The application became a permanent feature in research labs in no time at all. Dr. Jinek studied at Trinity College (Cambridge University) and completed a doctorate in Heidelberg. He moved to the University of Zurich from the University of Berkeley in the United States two years ago. “The university’s good reputation and the outstanding research environment were key factors in the move to Switzerland,” says Dr. Jinek. Meanwhile, he has already been awarded a prestigious ERC grant worth millions from the European Research Council and won the John Kendrew Prize from the European Molecular Biology Laboratory in Heidelberg. The Friedrich Miescher Prize is Switzerland’s top accolade for outstanding achievements in biochemistry. The prize-winners must be younger than 40, hold Swiss citizenship or have conducted their research in Switzerland.

High Salt Intake Accelerates Chronic Kidney Disease by Activating Renin-Angiotensin Axis

In addition to affecting blood pressure, high salt intake can promote kidney function decline in patients with chronic kidney disease. A study appearing in online on January 29,2015 in the Journal of the American Society of Nephrology (JASN) reveals that the effects of salt consumption on the kidneys are mediated at least in part by brain-kidney interactions. The findings suggest new strategies for protecting patients' kidney health. While it is known that salt intake can contribute to the progression of chronic kidney disease, the mechanisms involved are unclear. Fan Fan Hou, M.D., Ph.D., Wei Cao, M.D., and Aiqing Li, Ph.D. (Southern Medical University, in Guangzhou, China) wondered whether interactions between the kidneys and the brain might be involved. Their research team studied the brain-kidney connections in rats with kidney disease. The investigators found that salt intake accelerated kidney scarring in the animals by activating a brain-kidney connection called the renin-angiotensin axis that interlinks the damaged kidney and brain by afferent and efferent sympathetic nerves. Targeting these nerves reduced salt-induced kidney scarring. "These findings provide novel targets to fill a therapeutic void in preventing relentless progression of chronic kidney disease," said Dr. Hou. The investigators noted that kidney scarring, or fibrosis, is the final common pathway for most categories of chronic kidney disease and culminates in kidney failure. Additional co-authors of the study included Liangliang Wang, M.D.; Zhanmei Zhou, M.B.B.S.; Zhengxiu Su, M.Med.; Wei Bin, M.B.B.S.; and Christopher Wilcox, M.D., Ph.D. The article was entitled "A Salt-Induced Reno-Cerebral Reflex Activates Renin-Angiotensin Systems and Promotes CKD Progression."

Crucial Protective Role Observed for Farnesoid-X Receptor in Cholestatic Liver Injury

The farnesoid-X receptor (FXR) (image), also known as the chief regulator of bile acid metabolism, is thought to play a role in some hepatobiliary and gastrointestinal disorders. In a study published online on January 11, 2015 in The American Journal of Pathology, researchers demonstrated dysfunctional intestinal FXR-signaling in a rat model of cholestatic liver injury, accompanied by intestinal bacterial translocation (BTL) and increased permeability and inflammation. Notably, a highly potent, selective FXR agonist, obeticholic acid (INT-747), counteracted these effects, suggesting a potential new therapeutic avenue for liver disease. FXR has been recognized as a key transcription-regulator in hepatic and intestinal bile metabolism. “In experimental cholestasis, FXR-agonism improves ileal barrier function by attenuating intestinal inflammation leading to reduced bacterial translocation, demonstrating a crucial protective role for FXR in the gut-liver axis,” said lead investigator Len Verbeke, M.D., Ph.D., of the Division of Liver and Biliopancreatic Disorders at University Hospitals Leuven, KU Leuven-University of Leuven, Belgium. The experimental model used generated cholestatic liver injury in rats (cholestasis refers to a condition in which the flow of bile is blocked). In one experiment, 51 rats underwent ligation of the common bile duct (BDL) and were then treated with vehicle, 5 mg/kg ursodeoxycholic acid (UDCA), or 5 mg/kg of the FXR agonist INT-747 by gavage every two days for 10 days after surgery. UDCA is a bile acid similar in molecular structure to INT-747, which lacks FXR-agonizing properties. INT-747 is a semisynthetic bile acid derivative that is a first-in-class FXR agonist.