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I copy news articles pertaining to research, news and information for Parkinson's disease, Dementia, the Brain, Depression and Parkinson's with Dystonia. I also post about Fundraising for Parkinson's disease and events. I try to be up-to-date as possible. I have Parkinson's diseases as well and thought it would be nice to have a place where updated news is in one place. That is why I began this blog.
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Saturday, February 20, 2016
Friday, February 19, 2016
Feb. 19, 2016
Lausanne, Switzerland (Scicasts) — Researchers led by EPFL have found how lactate, a waste product of glucose metabolism can protect neurons from damage following acute trauma such as stroke or spinal cord injury.
Stroke or spinal cord injury can cause nerve cells to receive excessive stimulation, which ultimately damages and even kills them. This process is known as excitotoxicity, and it is one of the reasons why time following such trauma is critical, while it also implicated in progressive neurodegenerative diseases, e.g. Alzheimer's .
A team of scientists led by EPFL has now discovered that lactate, which is produced in the brain and even muscles after intense exercise, can be used to protect neurons against excitotoxicity. The study is published in the Nature journal Scientific Reports.
Step-by-step description of how lactate protects neurons against excitotoxicity: (1) Excessive glutamate activity triggers a strong influx of calcium (Ca2+) into the neuron through NMDA receptors, which leads to cell death. (2) Lactate is transported into the neuron and (3) converted to pyruvate by the enzyme lactate dehydrogenase (LDH). (4) Pyruvate is then transported into mitochondria by the mitochondrial pyruvate carrier (MPC) where it generates ATP. (5) ATP is then released through pannexins and activates the receptor P2Y, which (6) activates the PI3K pathway. (7) This triggers the opening of potassium channels (K+), which causes the neuron to hyperpolarize, decreasing the neuron's excitability, and thus protecting it from excitotoxic damage. Image: Pascal Jourdain (EPFL)
Following acute trauma such as a stroke or spinal cord injury, a certain type of receptors go into overdrive and overwhelm the target neuron with a barrage of electrical signals. This causes a build-up of calcium ions inside the neuron, which triggers toxic biochemical pathways that ultimately damage or kill it.
The receptors that cause this are called NMDA receptors, and interact with the neurotransmitter glutamate. NMDA receptors are a major target in research and medicine, as they are implicated in a number of disorders, including epilepsy, schizophrenia, and even Alzheimer's.
A team of researchers led by Pierre Magistretti from EPFL and the King Abdullah University of Science and Technology, investigated the effects of glutamate on cultured neurons from the brains of mice. The scientists used a new, non-invasive imaging technique called Digital Holographic Microscopy that can visualize cells structure and dynamics with nanometer-level resolution.
Previous studies have suggested that, lactate could protect neurons against excitotoxicity. Lactate is produced in the brain and in muscles after intense exercise as a waste product of glucose metabolism. Nonetheless, how lactate protects neurons has eluded scientists until now.
The researchers tested the effects of glutamate on the mouse neurons with and without lactate. The results were revealing: glutamate killed 65% of the neurons, but when with lactate, that number dropped to 32%.
The researchers then aimed to determine how lactate protects neurons. By using different receptor blockers on the mouse neurons, they determined that lactate triggers the production of ATP, the cell's energy molecule. In turn, the produced ATP binds and activates another type of receptor in the neuron, which turns on a complex cascade of defense mechanisms. As a result, the neuron can withstand the onslaught of signals from the NMDA receptor.
The breakthrough can advance our understanding of neuroprotection, which could lead to improved pharmacological ways to ameliorate the irreparable damage caused by stroke, spinal cord injury, and other trauma.
Article adapted from a École Polytechnique Fédérale de Lausanne news release.
Publication: L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade. Jourdain, P et al. Scientific Reports (19 February, 2016).
admin February 19, 2016
Leg pain can be significant and have many causes; some related to Parkinson’s disease, some that increase in frequency with age and others that are more common in both conditions. Here are just a few:
Pain associated with Parkinson’s
▪ Off related pain – diffuse aching and/or throbbing pain that increases at end of dopaminergic medicine dosing or when medication levels are low. Unlike joint pain, this pain is often located in the muscle such as the thigh or calf but not the knee of ankle. PD medications can often improve this pain.
▪ Restless leg syndrome – uncomfortable sensations most commonly felt in legs that is worse at night and while resting and relieved with movement. See related post on restless leg syndrome for more information.
▪ Dystonia-involuntary contraction of muscle. This can be common as a symptom of PD, an off related symptom or as a form of dyskinesia from medication. An example is early morning foot dystonia described as painful cramping of the toes and feet. Botulinum toxin (Botox, Myobloc) therapy can help
▪ Arthritis of the knee, hip or ankle typically causes pain in the join and not muscle. Although this is unrelated to PD, arthritic pain can worsen when the natural biomechanics of the joint is altered with PD rigidity, loss of strength and loss of flexible. Physical therapy and anti-inflammatory agents are an important treatment for this and the condition described next.
▪ Achilles tendonitis is pain located at the ankle and plantar faciitis is pain located under the sole of the foot. Both conditions can flare with a change in exercise routine, with improper stretching and secondary to the tightness of the ankle and foot often found in PD.
▪ Peripheral neuropathy is caused by nerve damage that begins in the feet. Associated symptoms are pain, burning, numbness and tingling. The most common causes are aging, diabetes, vitamin B12, deficiency, thyroid deficiency and blood protein disorders. this condition not only causes pain but also can worsen balance. Blood tests can help identify the cause of this problem.
▪ Radiculopathy or sciatic nerve compression can cause pain in the thigh, calf in foot depending on the nerves affected. Causes could include arthritis and disk disease of the spin and compression of the sciatic nerve in the buttock region due to muscle tightness,
Spinal stenosis is a problem of narrowing of the spinal canal. Often associated with back pain and pain in both legs. this type of pain often improves when a person is bent forward.
Leg swelling can occur with PD, medications and other medical conditions. Abrupt change in leg swelling associated with pain could be a sign of a blood clot requiring immediate medical attention. Lack of movement and dehydration can increase this risk in PD.
This information does not represent all types of pain that can occur. As always, be sure to talk with your healthcare provider if you are experiencing pain in your legs.
Monique L. Giroux, MD
Guest Blogger, Former Medical Director of NWPF