Posts tagged noradrenaline
Articles and news from the latest research reports.
(Image caption: In this image, marking shows the axons in retinal neurons (in red) that innervate the superior colliculus (in blue) in a “normal” mouse. Credit: © Michael Reber / Institut des Neurosciences Cellulaires et Intégratives)
Confirmation of the neurobiological origin of attention-deficit disorder
A study, carried out on mice, has just confirmed the neurobiological origin of attention-deficit disorder (ADD), a syndrome whose causes are poorly understood. Researchers from CNRS, the University of Strasbourg and INSERM1 have identified a cerebral structure, the superior colliculus, where hyperstimulation causes behavior modifications similar to those of some patients who suffer from ADD. Their work also shows noradrenaline accumulation in the affected area, shedding light on this chemical mediator having a role in attention disorders. These results are published in the journal Brain Structure and Function.
Attention-deficit disorder affects between 4-8% of children. It manifests mainly through disturbed attention and verbal and motor impulsiveness, sometimes accompanied by hyperactivity. About 60% of these children still show symptoms in adulthood. No cure exists at this time. The only effective treatment is to administer psychostimulants, but these have substantial side effects, such as dependence. Persistent controversy surrounding the neurobiological origin of this disorder has hindered the development of new treatments.
The study in Strasbourg investigated the behavior of transgenic mice having developmental defects in the superior colliculus. This structure, located in the midbrain, is a sensory hub involved in controlling attention and visual and spatial orientation. The mice studied were characterized by duplicated neuron projections between the superior colliculus and the retina. This anomaly causes visual hyperstimulation and excess noradrenaline in the superior colliculus. The effects of the neurotransmitter noradrenaline, which vary from species to species, are still poorly understood. However, we do know that this noradrenaline imbalance is associated with significant behavioral changes in mice carrying the genetic mutation. By studying them, researchers have observed a loss of inhibition: for example mice hesitate less to penetrate a hostile environment. They have difficulties in understanding relevant information and demonstrate a form of impulsiveness. These symptoms remind us of adult patients suffering from one of the forms of ADD.
Currently, the fundamental work on ADD uses mainly animal models obtained by mutations that disturb dopamine production and transmission pathways. In mice with a malformed superior colliculus, these pathways are intact. The changes occur elsewhere in the neural networks of the midbrain. By broadening the classic boundary used to research its causes, using these new models would allow a more global approach to ADD to be developed. Characterizing the effects of noradrenaline on the superior colliculus more precisely could open the way to innovative therapeutic strategies.
Brain may flush out toxins during sleep
NIH-funded study suggests sleep clears brain of molecules associated with neurodegeneration
A good night’s rest may literally clear the mind. Using mice, researchers showed for the first time that the space between brain cells may increase during sleep, allowing the brain to flush out toxins that build up during waking hours. These results suggest a new role for sleep in health and disease. The study was funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the NIH.
“Sleep changes the cellular structure of the brain. It appears to be a completely different state,” said Maiken Nedergaard, M.D., D.M.Sc., co-director of the Center for Translational Neuromedicine at the University of Rochester Medical Center in New York, and a leader of the study.
For centuries, scientists and philosophers have wondered why people sleep and how it affects the brain. Only recently have scientists shown that sleep is important for storing memories. In this study, Dr. Nedergaard and her colleagues unexpectedly found that sleep may be also be the period when the brain cleanses itself of toxic molecules.
Their results, published in Science, show that during sleep a “plumbing” system, called the glymphatic system, may open, letting fluid flow rapidly through brain. Dr. Nedergaard’s lab recently discovered the glymphatic system helps control whether cerebrospinal fluid (CSF), a clear liquid surrounding the brain and spinal cord, flows through the brain.
“It’s as if Dr. Nedergaard and her colleagues have uncovered a network of hidden caves and these exciting results highlight the potential importance of the network in normal brain function,” said Roderick Corriveau, Ph.D., a program director at NINDS.
Initially the researchers studied the system by injecting dye into the CSF of mice and watching it flow through their brains while simultaneously monitoring electrical brain activity. The dye flowed rapidly when the mice were unconscious, either asleep or anesthetized. In contrast, the dye barely flowed when the same mice were awake.
“We were surprised by how little flow there was into the brain when the mice were awake,” said Dr. Nedergaard. “It suggested that the space between brain cells changed greatly between conscious and unconscious states.”
To test this idea, the researchers inserted electrodes into the brain to directly measure the space between brain cells. They found that the space inside the brains increased by 60 percent when the mice were asleep or anesthetized.
“These are some dramatic changes in extracellular space,” said Charles Nicholson, Ph.D., a professor at New York University’s Langone Medical Center and an expert in measuring the dynamics of brain fluid flow and how it influences nerve cell communication.
Certain brain cells, called glia, control flow through the glymphatic system by shrinking or swelling. Noradrenaline is an arousing hormone that is also known to control cell volume. Treating awake mice with drugs that block noradrenaline induced sleep and increased brain fluid flow and the space between cells, further supporting the link between the glymphatic system and sleep.
Previous studies suggest that toxic molecules involved in neurodegenerative disorders accumulate in the space between brain cells. In this study, the researchers tested whether the glymphatic system controls this by injecting mice with radiolabeled beta-amyloid, a protein associated with Alzheimer’s disease, and measuring how long it lasted in their brains when they were asleep or awake. Beta-amyloid disappeared faster in mice brains when the mice were asleep, suggesting sleep normally clears toxic molecules from the brain.
“These results may have broad implications for multiple neurological disorders,” said Jim Koenig, Ph.D., a program director at NINDS. “This means the cells regulating the glymphatic system may be new targets for treating a range of disorders.”
The results may also highlight the importance of sleep.
“We need sleep. It cleans up the brain,” said Dr. Nedergaard.
(Source: ninds.nih.gov)
Scientists shed light on the brain mechanisms behind a debilitating sleep disorder
Researchers at the University of Toronto discover how the body’s muscles accidentally fall asleep while awake
Normally muscles contract in order to support the body, but in a rare condition known as cataplexy the body’s muscles “fall asleep” and become involuntarily paralyzed. Cataplexy is incapacitating because it leaves the affected individual awake, but either fully or partially paralyzed. It is one of the bizarre symptoms of the sleep disorder called narcolepsy.
“Cataplexy is characterized by muscle paralysis during cognitive awareness, but we didn’t understand how this happened until now, said John Peever of the University of Toronto’s Department of Cell & Systems Biology. “We have shown that the neuro-degeneration of the brain cells that synthesize the chemical hypocretin causes the noradrenaline system to malfunction. When the norandrenaline system stops working properly, it fails to keep the motor and cognitive systems coupled. This results in cataplexy – the muscles fall asleep but the brain stays awake.”
Peever and Christian Burgess, also of Cell & Systems Biology used hypocretin-knockout mice (mice that experience cataplexy), to demonstate that a dysfunctional relationship between the noradrenaline system and the hypocretin-producing system is behind cataplexy. The research was recently published in the journal Current Biology.
The scientists first established that mice experienced sudden loss of muscle tone during cataplectic episodes. They then administered drugs to systematically inhibit or activate a particular subset of adrenergic receptors, the targets of noradrenaline. They were able to reduce the incidence of cataplexy by 90 per cent by activating noradrenaline receptors. In contrast, they found that inhibiting the same receptors increased the incidence of cataplexy by 92 per cent. Their next step was to successfully link how these changes affect the brain cells that directly control muscles.
They found that noradrenaline is responsible for keeping the brain cells (motoneurons) and muscles active. But during cataplexy when muscle tone falls, noradrenaline levels disappear. This forces the muscle to relax and causes paralysis during cataplexy. Peever and Burgess found that restoring noradrenaline pre-empted cataplexy, confirming that the noradrenaline system plays a key role.
(Source: media.utoronto.ca)