From ScienceDaily website (see original article)
July 26, 2013 — The results of a new study by neurological researchers at Rush University Medical Center show that a sudden decrease of testosterone, the male sex hormone, may cause Parkinson's like symptoms in male mice.
The findings were recently published in the Journal of Biological Chemistry.
One of the major roadblocks for discovering drugs against Parkinson's disease is the unavailability of a reliable animal model for this disease.
"While scientists use different toxins and a number of complex genetic approaches to model Parkinson's disease in mice, we have found that the sudden drop in the levels of testosterone following castration is sufficient to cause persistent Parkinson's like pathology and symptoms in male mice," said Dr. Kalipada Pahan, lead author of the study and the Floyd A. Davis endowed professor of neurology at Rush.
"We found that the supplementation of testosterone in the form of 5-alpha dihydrotestosterone (DHT) pellets reverses Parkinson's pathology in male mice."
"In men, testosterone levels are intimately coupled to many disease processes," said Pahan.
Typically, in healthy males, testosterone level is the maximum in the mid-30s, which then drop about one percent each year.
However, testosterone levels may dip drastically due to stress or sudden turn of other life events, which may make somebody more vulnerable to Parkinson's disease.
"Therefore, preservation of testosterone in males may be an important step to become resistant to Parkinson's disease," said Pahan.
Understanding how the disease works is important to developing effective drugs that protect the brain and stop the progression of Parkinson's disease.
Nitric oxide is an important molecule for our brain and the body.
"However, when nitric oxide is produced within the brain in excess by a protein called inducible nitric oxide synthase, neurons start dying," said Pahan.
"This study has become more fascinating than we thought," said Pahan.
"After castration, levels of inducible nitric oxide synthase (iNOS) and nitric oxide go up in the brain dramatically.
Interestingly, castration does not cause Parkinson's like symptoms in male mice deficient in iNOS gene, indicating that loss of testosterone causes symptoms via increased nitric oxide production."
"Further research must be conducted to see how we could potentially target testosterone levels in human males in order to find a viable treatment," said Pahan.
giovedì 5 settembre 2013
Migraines Associated With Variations in Structure of Brain Arteries
From ScienceDaily website (see original article)
July 26, 2013 — The network of arteries supplying blood flow to the brain is more likely to be incomplete in people who suffer migraine, a new study by researchers in the Perelman School of Medicine at the University of Pennsylvania reports.
Variations in arterial anatomy lead to asymmetries in cerebral blood flow that might contribute to the process triggering migraines.
The arterial supply of blood to the brain is protected by a series of connections between the major arteries, termed the "circle of Willis" after the English physician who first described it in the 17th century.
People with migraine, particularly migraine with aura, are more likely to be missing components of the circle of Willis.
Migraine affects an estimated 28 million Americans, causing significant disability.
Experts once believed that migraine was caused by dilation of blood vessels in the head, while more recently it has been attributed to abnormal neuronal signals.
In this study, appearing in PLOS ONE, researchers suggest that blood vessels play a different role than previously suspected: structural alterations of the blood supply to the brain may increase susceptibility to changes in cerebral blood flow, contributing to the abnormal neuronal activity that starts migraine.
"People with migraine actually have differences in the structure of their blood vessels -- this is something you are born with," said the study's lead author, Brett Cucchiara, MD, Associate Professor of Neurology.
"These differences seem to be associated with changes in blood flow in the brain, and it's possible that these changes may trigger migraine, which may explain why some people, for instance, notice that dehydration triggers their headaches."
In a study of 170 people from three groups -- a control group with no headaches, those who had migraine with aura, and those who had migraine without aura -- the team found that an incomplete circle of Willis was more common in people with migraine with aura (73 percent) and migraine without aura (67 percent), compared to a headache-free control group (51 percent).
The team used magnetic resonance angiography to examine blood vessel structure and a noninvasive magnetic resonance imaging method pioneered at the University of Pennsylvania, called Arterial spin labeling (ASL), to measure changes in cerebral blood flow.
"Abnormalities in both the circle of Willis and blood flow were most prominent in the back of the brain, where the visual cortex is located.
This may help explain why the most common migraine auras consist of visual symptoms such as seeing distortions, spots, or wavy lines," said the study's senior author, John Detre, MD, Professor of Neurology and Radiology.
Both migraine and incomplete circle of Willis are common, and the observed association is likely one of many factors that contribute to migraine in any individual.
The researchers suggest that at some point diagnostic tests of circle of Willis integrity and function could help pinpoint this contributing factor in an individual patient.
Treatment strategies might then be personalized and tested in specific subgroups.
July 26, 2013 — The network of arteries supplying blood flow to the brain is more likely to be incomplete in people who suffer migraine, a new study by researchers in the Perelman School of Medicine at the University of Pennsylvania reports.
Variations in arterial anatomy lead to asymmetries in cerebral blood flow that might contribute to the process triggering migraines.
The arterial supply of blood to the brain is protected by a series of connections between the major arteries, termed the "circle of Willis" after the English physician who first described it in the 17th century.
People with migraine, particularly migraine with aura, are more likely to be missing components of the circle of Willis.
Migraine affects an estimated 28 million Americans, causing significant disability.
Experts once believed that migraine was caused by dilation of blood vessels in the head, while more recently it has been attributed to abnormal neuronal signals.
In this study, appearing in PLOS ONE, researchers suggest that blood vessels play a different role than previously suspected: structural alterations of the blood supply to the brain may increase susceptibility to changes in cerebral blood flow, contributing to the abnormal neuronal activity that starts migraine.
"People with migraine actually have differences in the structure of their blood vessels -- this is something you are born with," said the study's lead author, Brett Cucchiara, MD, Associate Professor of Neurology.
"These differences seem to be associated with changes in blood flow in the brain, and it's possible that these changes may trigger migraine, which may explain why some people, for instance, notice that dehydration triggers their headaches."
In a study of 170 people from three groups -- a control group with no headaches, those who had migraine with aura, and those who had migraine without aura -- the team found that an incomplete circle of Willis was more common in people with migraine with aura (73 percent) and migraine without aura (67 percent), compared to a headache-free control group (51 percent).
The team used magnetic resonance angiography to examine blood vessel structure and a noninvasive magnetic resonance imaging method pioneered at the University of Pennsylvania, called Arterial spin labeling (ASL), to measure changes in cerebral blood flow.
"Abnormalities in both the circle of Willis and blood flow were most prominent in the back of the brain, where the visual cortex is located.
This may help explain why the most common migraine auras consist of visual symptoms such as seeing distortions, spots, or wavy lines," said the study's senior author, John Detre, MD, Professor of Neurology and Radiology.
Both migraine and incomplete circle of Willis are common, and the observed association is likely one of many factors that contribute to migraine in any individual.
The researchers suggest that at some point diagnostic tests of circle of Willis integrity and function could help pinpoint this contributing factor in an individual patient.
Treatment strategies might then be personalized and tested in specific subgroups.
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