Keeping you up to date on recent headlines in neurology.
Scientists develop mathematical model to assist Parkinson's research ... Australian scientists have significantly advanced our understanding of dopamine release from nerve cells, findings that should speed the development of more effective drugs for treating Parkinson's Disease. People with Parkinson's suffer from muscle rigidity, tremor, a slowing of physical movement and, in extreme cases, a loss of physical movement. These primary symptoms are caused by the loss of dopamine producing nerve cells in the brain. Medicines used for treating Parkinson's either provide extra dopamine or attach to the remaining nerve cells that release dopamine and regulate its release. In the latter case, no-one understands the mechanisms involved, or how to control them. Neuroscientists at Garvan Institute of Medical Research (Sydney) have developed a mathematical model and microscopy method that reveal the mechanisms behind synaptic dopamine release and the factors that govern the probability of release. These findings, made by Drs. James Daniel and Bryce Vissel, are now published online in the Journal of Neuroscience. "While there has been an enormous amount of effort put into the development of drugs for Parkinson's, very little has been known about how the dopamine releasing drugs achieve their effects, other than the fact they attach to a receptor on a dopamine nerve cell, and then something happens," said Vissel. According to Vissel, we are still in the dark ages in understanding the sub-microscopic events that take place in the brain. "We have roughly 100 billion nerve cells in our brains, with up to 100,000 connections each. We're only just beginning to understand that every connection is regulated in the most extraordinarily sophisticated way," he said.
Synaptic activity understanding may support Huntington's Disease theory ... Investigators at Burnham Institute for Medical Research (La Jolla, California), the University of British Columbia's Centre for Molecular Medicine and Therapeutics (Vancouver) and the University of California, San Diego have found that normal synaptic activity in nerve cells (the electrical activity in the brain that allows nerve cells to communicate with one another) protects the brain from the misfolded proteins associated with Huntington's disease. In contrast, excessive extrasynaptic activity (aberrant electrical activity in the brain, usually not associated with communication between nerve cells) enhances the misfolded proteins' deadly effects. Researchers also found that the drug Memantine, which is approved to treat Alzheimer's disease, successfully treated Huntington's disease in a mouse model by preserving normal synaptic electrical activity and suppressing excessive extrasynaptic electrical activity. The research is published in the journal Nature Medicine. In the new study, researchers initially tested nerve cell cultures transfected with mutant Huntingtin protein and found that reducing excessive NMDA-type glutamate receptor activity with Memantine and other antagonists protected the nerve cells (glutamate receptors are the main trigger of excitatory electrical activity in the brain but in excess can cause nerve cell death, a process called excitotoxicity). They also found that normal synaptic activity was protective. Subsequently, they treated Huntington's disease model mice with both high and low doses of Memantine and found that the low doses were protective by blocking pathological extrasynaptic activity, while high-dose Memantine encouraged disease progression because it also blocked the protective synaptic NMDA receptor activity. Huntington's disease is a hereditary condition caused by a mutated huntingtin gene that creates a misfolded, and therefore dysfunctional, protein. The new research shows that normal synaptic receptor activity makes nerve cells more resistant to the mutant proteins. However, excessive extrasynaptic activity contributed to increased nerve cell death. The research team found that low doses of Memantine reduce extrasynaptic activity without impairing protective synaptic activity.
Dementia study to continue work for five more years... Every two years, 2,000 senior Group Health patients check in with the Adult Changes in Thought (ACT) study. The joint project between Group Health Research Institute and the University of Washington (both Seattle) focuses on finding ways to delay or prevent dementia, including Alzheimer's disease, and declines in memory and thinking. It aims to deepen understanding of how the body - especially the brain - ages. The National Institute on Aging recently awarded the ACT study a grant of nearly $12 million to continue its work for the next five years. In continuous operation for 23 years, it is the longest-running study of its kind. At each biannual study visit, participants are observed as they walk and do many other physical and mental tasks. They are asked many questions, including whether they would allow an autopsy on their brains after they die. Thanks to willing participants, the study has gleaned its most recent discoveries, which center on how vascular (blood vessel) disease contributes to late-life dementia, including Alzheimer's disease:
• Microscopic injuries to blood vessels in the brain, called cerebral "microinfarcts," which cause "small-vessel disease of the brain," can lead to many brain problems in late life.
• These microinfarcts may be responsible for more cases of dementia than previously recognized, often combined with Alzheimer's.
• Controlling high blood pressure may lower the risk of dementia by minimizing microinfarcts.
In the next five years, the ACT team will largely focus on deeper exploration of these most recent findings. They will test whether diabetes, kidney disease, and atrial fibrillation (the most common abnormal heart rhythm) contribute to brain decline through microinfarcts or changes in larger blood vessels - and whether physical activity counters them. Ongoing trials also include interventions to improve sleep as well as thinking and physical well-being.
MJF Foundation awards grant for Parkinson's research ... Beth Israel Deaconess Medical Center (BIDMC; Boston) neurologists Alvaro Pascual-Leone, MD, PhD, and Daniel Tarsy, MD, have been awarded grants totaling more than $1.5 million from the Michael J. Fox Foundation for Parkinson's Research (MJFF) to conduct investigations aimed at improving the quality of life for patients with Parkinson's disease. Pascual-Leone, Director of BIDMC's Berenson-Allen Center for Noninvasive Brain Stimulation, will oversee a three-year $1.498 million grant to investigate the use of repetitive transcranial magnetic stimulation (rTMS) therapy to control symptoms of Parkinson's disease. As part of the study, 160 patients will be enrolled in clinical trials at BIDMC and at three other North American centers including the University of Florida (Gainesville), the University of California in Los Angeles, and the Toronto Western Research Institute-University of Toronto. "Depression is very common among patients with Parkinson's disease and evidence suggests that it is not merely a response to chronic illness or motor impairments but, in fact, results from factors related to the degenerative brain process itself," said Pascual-Leone, whose pioneering work has demonstrated that TMS therapy in which a mild electric current is delivered through a magnetic coil placed over a patient's scalp to help adjust brain signals that have gone awry can successfully treat depression in patients who have not responded to other therapies.
—Compiled by Rob Kimball, MDD