Breaking News
September 25, 2018 - Vaping among kids and teens a growing concern
September 25, 2018 - Public launch of products and application solutions from Porvair Laboratory Division
September 25, 2018 - Harmful H. pylori may play a role in Parkinson’s disease
September 25, 2018 - Researchers develop way to measure different types of fear of falling in patients with Parkinson’s
September 25, 2018 - Fracture causes bone density losses throughout the body
September 25, 2018 - Researchers highlight potential therapy for treating rare, deadly blood-clotting disorder
September 25, 2018 - Hybrid theranostic complex shows high therapeutic efficacy against tumor cells
September 25, 2018 - FDA Issues Statement Reaffirming the Positive Benefit-Risk Profile of Nuplazid (pimavanserin) for Patients with Hallucinations and Delusions Associated with Parkinson’s Disease Psychosis
September 25, 2018 - Toxicological evaluation and dosimetry estimation of potential PET radiotracer
September 25, 2018 - 5 obstacles parents commonly face in child obesity treatment and how to overcome them
September 25, 2018 - Immunologist to study how Chikungunya causes devastating effects in older adults
September 25, 2018 - Rural borderland communities vulnerable to high stress impacting mental and physical health
September 25, 2018 - SNMMI announces recipients of 2018-2020 Wagner-Torizuka Fellowship
September 25, 2018 - Common painkiller not effective in controlling chronic pain after traumatic nerve injury
September 25, 2018 - New therapeutic vaccine helps immune cells fight HPV-related head and neck cancer
September 25, 2018 - Environmentally-induced gene activity influences IQ test performance
September 25, 2018 - Biogen and Eisai announce results of LTE Phase 1b study of aducanumab for treating MCI
September 25, 2018 - FDA Approves Copiktra (duvelisib) Capsules for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Follicular Lymphoma
September 25, 2018 - Medical device company settles US case over false claims
September 25, 2018 - Trying to get answers: One woman’s quest for a diagnosis
September 25, 2018 - Lung cancer patients treated with invasive surgery more likely to become chronic opioid users
September 25, 2018 - Oxford VR raises £3.2m to boost innovation in VR for mental health problems
September 25, 2018 - Gene therapy approach could help treat mitochondrial diseases
September 25, 2018 - Few Yogurt Products Qualify As Low-Sugar
September 25, 2018 - Eye disease can cause blindness, and it’s on the rise
September 25, 2018 - Pawnshop density linked to gun-related suicides, Stanford study finds
September 25, 2018 - Pioneering procedure for common prostate condition offered by The London Clinic
September 25, 2018 - Number of people with respiratory diseases likely to increase if UK air pollution remains unchecked
September 25, 2018 - FARXIGA receives positive results in Phase III DECLARE-TIMI 58 cardiovascular outcomes trial
September 25, 2018 - New program to reduce harmful stress effectively improves mood in cancer patients
September 24, 2018 - Florence’s Lingering Threat: Mold – Drugs.com MedNews
September 24, 2018 - For professional baseball players, faster hand-eye coordination linked to batting performance
September 24, 2018 - Bill for later school start times is defeated, but Stanford sleep specialist isn’t
September 24, 2018 - For Heart Failure Patients, Mitral Valve Procedure Improved Outcomes
September 24, 2018 - Successful recovery from addiction means more than achieving abstinence
September 24, 2018 - New nanoplatform technology may reverse drug-resistance in renal cell carcinoma
September 24, 2018 - October 1918 marks the centenary of Spanish Flu that claimed more lives than World War I
September 24, 2018 - LGBT community reports more number of poor mental health days than general population
September 24, 2018 - New research suggests power of zebrafish as tool for cancer drug discovery
September 24, 2018 - New study finds height as possible risk factor for developing varicose veins
September 24, 2018 - Researchers compare weight loss results of online and in-person diabetes prevention program
September 24, 2018 - New HER2 PET Study Uses Affibody’s ABY-025 Tracer to Individualize Breast Cancer Treatment
September 24, 2018 - Drug combination offers more effective care for patients suffering miscarriage
September 24, 2018 - Tallness linked to varicose veins, Stanford study says
September 24, 2018 - For Heart Failure Patients, Mitral Valve Procedure Improved Outcomes
September 24, 2018 - Ecstasy drug makes octopuses more social
September 24, 2018 - Immediate compression therapy could cut risk of complications after deep-vein thrombosis
September 24, 2018 - Transcatheter mitral valve repair reduces mortality for patients with mitral regurgitation
September 24, 2018 - First intracranial aneurysm patients treated with BRAVO Flow Diverter after CE mark approval
September 24, 2018 - ‘Physicians of the mouth’? Dentists absorb the medical billing drill
September 24, 2018 - People more likely to believe those with confident tone of voice than with accent
September 24, 2018 - Harmony Biosciences Presents 5-Year Data On Pitolisant At International Narcolepsy Symposium
September 24, 2018 - Blood test may identify gestational diabetes risk in first trimester
September 24, 2018 - Height may be risk factor for varicose veins | News Center
September 24, 2018 - King’s commemorates opening of new NMR facility with one-day symposium
September 24, 2018 - Eisai receives approval for partial label change of DC Bead device for transcatheter arterial embolization
September 24, 2018 - Using multi-level approach to reduce underage drinking among youths on rural reservations
September 24, 2018 - High-resolution genomic map gives scientists unprecedented view of brain development
September 24, 2018 - Researchers find impact of neurobehavioral symptoms on employment in adults with TBI
September 24, 2018 - Alexion announces positive results from Phase 3 PREVENT study of Soliris in patients with NMOSD
September 24, 2018 - First evaluation of benefits, harms of Alzheimer’s screening for family members of older adults
September 24, 2018 - Ancora Heart announces positive data of study evaluating AccuCinch Ventricular Repair System
September 24, 2018 - Children of mothers using cannabis may start using it at an earlier age, finds study
September 24, 2018 - Gilead Sciences plans to launch authorized generic versions of Epclusa and Harvoni in the US
September 24, 2018 - Most patients who underwent transcatheter valve replacement experience prosthesis-patient mismatch
September 24, 2018 - Lumos acquires license for LUM-201 drug that promotes secretion of growth hormone
September 24, 2018 - New study provides basis for Air Canada to change its facial hair policy for aircrew
September 24, 2018 - Infant walkers lead to thousands of emergency visits for babies
September 24, 2018 - Genes predicting person’s height may provide clues about causes of varicose veins
September 24, 2018 - EPA Plan Will Maintain Carbon Emissions From Power Plants
September 24, 2018 - Characterizing pig hippocampus could improve translational neuroscience
September 24, 2018 - Element3 Health reports social and mental engagement play key role in overall health
September 24, 2018 - Paralympic medalists support Fight for Sight’s unique virtual event
September 24, 2018 - ADCETRIS drug receives approval in Japan as frontline treatment option for Hodgkin lymphoma
September 24, 2018 - Public awareness of urological conditions found to be alarmingly low across Europe
September 24, 2018 - Fitter Folks Suffer Milder Strokes: Study
September 24, 2018 - Novel botulinum toxin compound relieves chronic pain
September 24, 2018 - CHMP recommends approval of Gilenya for treatment of multiple sclerosis in children, adolescents
September 24, 2018 - National Friendly’s private medical insurance is a hit with women living in the South East
September 24, 2018 - Academics receive prestigious awards for achievements in blood pressure research
Discovery offers fresh perspective on how the brain keeps its balance

Discovery offers fresh perspective on how the brain keeps its balance

image_pdfDownload PDFimage_print

As with all things in life, healthy brain function depends on a balance of forces. We think of our brains as active – moving a leg and saying a word are all “active” events. But it is just as important for our brains to be able to stop these actions -to stop our leg, and to stop our speech. But how do our brains actually perform the go/stop function?

In a recent study, an interdisciplinary team of scientists from The Hong Kong University of Science and Technology (HKUST) and The Chinese University of Hong Kong (CUHK) discovered that two large protein kinases, ATM and ATR, cooperate to help establish the go/stop balance.

The findings were published in the Journal Proceedings of the National Academy of Sciences on Jan 9, 2018 (doi: 10.1073/pnas.1716892115).

“Our discovery offers a fresh perspective on how our brain balances excitation and inhibition – basically “go” and “stop” of behavior,” said Aifang Cheng, first author of the paper. “We show that ATM and ATR regulate each other’s levels in the brain. When ATM levels drop, ATR levels increase and the reverse. Just as important, regular brain activity also changes the levels of the two proteins. This means that neuronal activity and the two kinases are in a dynamic ‘conversation’ that helps to keep the appropriate balance between excitation and inhibition (known as the E/I balance) by adjusting the levels of ATM and ATR.” Just as important, the team found that the two proteins divide up responsibilities for the ‘go’ and ‘stop’ functions. ATM helps regulate only excitatory events while ATR helps regulate only the inhibitory ones; this is achieved by controlling the movement of tiny synaptic vesicles in the neuronal synapse – the gap between two neurons that regulates information flow in the brain.

Utilizing super-resolution microscopy offered by the Super-Resolution Imaging Center (SRIC) at HKUST, the researchers were able to view the cellular location of the two kinases at ultra-high magnification. The custom designed super-resolution microscope with active stage locking provided the stability needed to obtain high-resolution images. The groups had previously worked together to show that ATM was found on synaptic vesicles, but no one had ever looked for ATR. Combining their efforts for a second time, the team was able to show that ATR was also on synaptic vesicles (identified with a protein called VAMP2).

“One of the challenges we faced was that even at high magnification, all vesicles look pretty much alike,” said Du Shengwang, physics professor and Associate Director of SRIC. “To provide differentiation, we developed a three-color version of our super-resolution system, which allowed the team to prove that ATM and ATR were never found on the same VAMP2-containing synaptic vesicle.”

The HKUST team then sent their findings to their collaborators at CUHK, where they produced crisp, high-resolution images of normal synapses and synapses from neurons that had no ATM protein. This allowed Cheng to measure the size of the synaptic vesicles, and she discovered that the vesicles without ATM were bigger than normal, a hint that there was a problem with the composition of the synaptic membrane.

“The new findings are in the realm of basic research, but they have important implications for human disease,” said Karl Herrup, Chair Professor and Head of the Division of Life Science at HKUST, Director of the SRIC and the senior author of the manuscript. “Epilepsy, for example, is a condition where one of the problems is that inhibition fails. As our findings would predict, humans with too little ATR have a problem with epilepsy, while people with ATM deficiency by contrast are ataxic – a reduced ability to make finely controlled movements and keep the proper E/I ratio. This means that there is a yin-yang relationship between ATM and ATR. And really, this is only the beginning. We believe that our work has potential relevance to a much broader range of neurologic conditions.”

Tagged with:

About author

Related Articles