Posts tagged neurotransmitters
Articles and news from the latest research reports.
Diuretic Drug Offers Latest Hope for Autism Treatment
A drug used for decades to treat high blood pressure and other conditions has shown promise in a small clinical trial for autism. The drug, bumetanide, reduced the overall severity of behavioral symptoms after 3 months of daily treatment. The researchers say that many parents of children who received the drug reported that their children were more “present” and engaged in social interactions after taking it. The new findings are among several recent signs that treatments to address the social deficits at the core of autism may be on the horizon.
Several lines of evidence suggest that autism interferes with the neurotransmitter GABA, which typically puts a damper on neural activity. Bumetanide may enhance the inhibitory effects of GABA, and the drug has been used safely as a diuretic to treat a wide range of heart, lung, and kidney conditions. In the new study, researchers led by Yehezkel Ben-Ari at the Mediterranean Institute of Neurobiology in Marseille, France, recruited 60 autistic children between the ages of 3 and 11 and randomly assigned them to receive either a daily pill of bumetanide or a placebo. (Neither the children’s parents nor the researchers who assessed the children knew who received the actual drug).
As a group, those who got bumetanide improved by 5.6 points on a 60-point scale that’s often used to assess behaviors related to autism, the researchers report today in Translational Psychiatry. That was enough to nudge the group average just under the cutoff for severe autism and into the mild to medium category. The study did not look directly at whether the drug improved all symptoms equally or some more than others. “We have some indications that the symptoms particularly ameliorated with bumetanide are the genuine core symptoms of autism, namely communication and social interactions,” Ben-Ari says. More work will be needed to verify that impression. Ben-Ari says his team is now preparing for a larger, multicenter trial in Europe.
Dopamine Not About Pleasure (Anymore)
To John Salamone, professor of psychology and longtime researcher of the brain chemical dopamine, scientific research can be very slow-moving.
“It takes a long time for things to change in science,” he says. “It’s like pulling on the steering wheel of an ocean liner, then waiting for the huge ship to slowly turn.”
Salamone has spent most of his career battling a particular long-held scientific idea: the popular notion that high levels of brain dopamine are related to experiences of pleasure. As increasing numbers of studies show, he says, the famous neurotransmitter is not responsible for pleasure, but has to do with motivation.
He summarizes and comments on the evidence for this shift in thinking in a Nov. 8 review in the Cell Press journal Neuron.
Neurotransmitters Linked to Mating Behavior Are Shared by Mammals and Worms
When it comes to sex, animals of all shapes and sizes tend to behave in predictable ways. There may be a chemical reason for that. New research from Rockefeller University has shown that chemicals in the brain — neuropeptides known as vasopressin and oxytocin — play a role in coordinating mating and reproductive behavior in animals ranging from humans to fish to invertebrates.
"Our research shows that molecules similar to vasopressin and oxytocin have an ancient and evolutionarily conserved role in controlling a critical social behavior, mating," says Cori Bargmann, Torsten N. Wiesel Professor and head of the Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior. "This work suggests that these molecules encode the same kind of information in the brains of very different animals."
Bargmann, whose laboratory studies the relationship between genes, neural circuits and behavior in the C. elegans roundworm, says vasopressin and oxytocin have been implicated in a variety of reproductive and social behaviors in humans and other mammals, including pair bonding, maternal bonding and aggressive and affiliative behaviors. Mice that lack oxytocin may develop social amnesia, and humans who sniff oxytocin through an inhaler change their cooperative behavior in computer games, behaving as though they “trust” other players more.
New clues to how the brain and body communicate to regulate weight
Maintaining a healthy body weight may be difficult for many people, but it’s reassuring to know that our brains and bodies are wired to work together to do just that—in essence, to achieve a phenomenon known as energy balance, a tight matching between the number of calories consumed versus those expended. This careful balance results from a complex interchange of neurobiological crosstalk within regions of the brain’s hypothalamus, and when this “conversation” goes awry, obesity or anorexia can result.
Given the seriousness of these conditions, it’s unfortunate that little is known about the details of this complex interchange. Now research led by investigators at Beth Israel Deaconess Medical Center (BIDMC) provides new insights that help bring order to this complexity. Described in the October 26 issue of the journal Cell, the findings demonstrate how the GABA neurotransmitter selectively drives energy expenditure, and importantly, also help explain the neurocircuitry underlying the fat-burning properties of brown fat.
"Our group has built up a research program with the overall goal of unraveling the ‘wiring diagram’ by which the brain controls appetite and the burning of calories," says senior author Bradford Lowell, MD, PhD, a Professor of Medicine in BIDMC’s Division of Endocrinology and Harvard Medical School. "To advance our understanding to this level, we need to know the function of specific subsets of neurons, and in addition, the upstream neurons providing input to, and the downstream neurons receiving output from, these functionally defined neurons. Until recently, such knowledge in the hypothalamus has been largely unobtainable."
Alzheimer Protein Seems to Slow Down Neurotransmitter Production
ScienceDaily (Aug. 21, 2012) — How abnormal protein deposits in the brains of Alzheimer’s patients disrupt the signalling between nerve cells has now been reported by researchers in Bochum and Munich, led by Dr. Thorsten Müller from the Medizinisches Proteom-Center of the Ruhr-Universität, in the journal Molecular and Cellular Proteomics. They varied the amount of APP protein and related proteins associated with Alzheimer’s disease in cell cultures, and then analysed how this manipulation affected other proteins in the cell. The result: the amount of APP present was related to the amount of an enzyme that is essential for the production of neurotransmitters and therefore for communication amongst nerve cells.
Mass spectrometer: The proteins are injected into the apparatus via a very thin needle. (Credit: © RUB-Pressestelle, Marion Nelle)
Proteomics: analysing all the proteins of the cells at once
Amyloid plaques are a characteristic feature of Alzheimer’s disease. They consist largely of cleavage products of the so-called amyloid precursor protein APP, which occur in excess in the brains of Alzheimer’s patients. What role APP plays in healthy people and why the abnormal accumulation of amyloid disrupts the regular functioning of the brain is still largely unclear. To understand the function of APP, the RUB researchers established a new cell model. The new cells produced only a very small amount of APP. What impact this had on all the other proteins of these cells was examined by the researchers through the use of mass spectrometry, among other things. With this method they identified over 2000 proteins and determined their concentrations. They were looking specifically for molecules whose concentrations in the newly established low-APP cells were different than in the reference cells that contained normal amounts of APP.
Abnormal protein able to curb neurotransmitter production
"One candidate has particularly caught our attention, this being the enzyme methionine adenosyltransferase II, alpha, MAT2A for short," Thorsten Müller said. Among other things, the enzyme is crucially involved in the production of neurotransmitters. Low-APP cells contained less MAT2A than the reference cells. To confirm the connection between the "Alzheimer’s protein" APP and the neurotransmitter-producing MAT2A, the team studied tissue samples from the brains of deceased Alzheimer’s patients and from healthy individuals. In the tissue of the Alzheimer’s patients there was less MAT2A than in the healthy samples. These results suggest that APP and MAT2A concentrations are related and are linked to the synthesis of neurotransmitters. "Our results point to a new mechanism by which the defective cleavage of the APP protein in Alzheimer’s disease could be directly related to altered neurotransmitter production," Müller said. "As a result, the signal transduction of nerve cells could be disrupted, which, over an extended period, could possibly also cause the death of cells."
Source: Science Daily
The mechanism of action of cocaine
Cocaine modifies the action of dopamine in the brain. The dopamine rich areas of the brain are the ventral tegmental area, the nucleus accumbens and the caudate nucleus – these areas are collectively known as the brain’s ‘reward pathway’. Cocaine binds to dopamine re-uptake transporters on the pre-synaptic membranes of dopaminergic neurones. This binding inhibits the removal of dopamine from the synaptic cleft and its subsequent degradation by monoamine oxidase in the nerve terminal. Dopamine remains in the synaptic cleft and is free to bind to its receptors on the post synaptic membrane, producing further nerve impulses. This increased activation of the dopaminergic reward pathway leads to the feelings of euphoria and the ‘high’ associated with cocaine use.
New Model Synapse Could Shed Light on Disorders Such as Epilepsy and Anxiety
A new way to study the role of a critical neurotransmitter in disorders such as epilepsy, anxiety, insomnia, depression, schizophrenia, and alcohol addiction has been developed by a group of scientists led by Gong Chen, an associate professor of biology at Penn State University.
The new method involves molecularly engineering a model synapse — a structure through which a nerve cell send signals to another cell. This model synapse can precisely control a variety of receptors for the neurotransmitter called GABA, which is important in brain chemistry. The research, which will be published in the Journal of Biological Chemistry on 10 August 2012, opens the door to the possibility of creating safer and more-efficient drugs that target GABA receptors and that cause fewer side effects.
What Caffeine Really Does to Your Brain
What caffeine does do is one heck of an impersonation. In your brain, caffeine is the quintessential mimic of a neurochemical called adenosine. Adenosine is produced by neurons throughout the day as they fire, and as more of it is produced, the more your nervous system ratchets down.
Your nervous system monitors adenosine levels through receptors, particularly the A1 receptor that is found in your brain and throughout your body. As the chemical passes through the receptors, your adenosine tab increases until your nervous system pays it off by putting you to sleep.