Archive for the ‘GABA’ Category

giant-rabbit
A petrified burglar fled a family home in the middle of the night – after coming face-to-face with their giant pet rabbit Toby.

Kimberley May, her fiance Martin, and their three-year-old daughter Olivia were all sound asleep when the thief broke into their house. But as the raider rifled through cupboards the noise woke up Toby the family’s British Giant bunny in his kitchen cage. The 4.5kg, two-feet long pet began stomping so loudly on the floor that the intruder was caught on the hop and left.

Kimberley said: “We went to bed on Wednesday at about 10pm. In the early hours of the morning Toby our rabbit did five loud thumps. “I sort of half woke up then realised he’d stopped and went back to sleep. When I went downstairs every single cupboard and drawer were open, there were bits out everywhere, then we started noticing things were missing and we phoned the police.”

Kimberley, a nurse, is convinced that two year-old Toby’s thumping scared the thief off from their house in Plymouth, Devon. She found a hoard of items left piled up on the sofa which she thinks the burglar was preparing to take but left behind.

She added: “Because of Christmas and my birthday just gone, I had loads of gift sets and perfumes that they’d laid out across the sofa. “We think that when the rabbit thumped it scared the burglar off and they left all the stuff they were going to take. He’s like a little dog, if you whistle him he comes. The rabbit was just traumatised in his cage, shaking. He’s usually really friendly but he tried to go for the policeman.”

The crook still managed to get away with other valuables including a treasured First World War medal that belonged to Kimberley’s great-grandad. Kimberley added: “They managed to take a laptop, an iPad and my handbag with my purse and everything in, but the worse thing was my great granddad’s medal. My gran actually died in 2007, she lived in a council house all her life, hardly had any possessions That was the one thing important thing she had. They also took a box which had all our wedding invitations and favours in it, as well as paperwork which I was due to give to the church and reception venue.”

Detective Constable Nick Bloom said: “We believe the family was burgled between 10.30pm on Wednesday February 6 and 7am on Thursday February 7. The police are asking for any witnesses or anyone with information to come forward.”

Toby still has some way to go before he is fully grown – British Giant rabbits can reach up to 5.9 kg.

Owner Kimberley, 30, said monster bunny Toby was so big he lives in a cage built for a Labrador. Kimberley and online salesman partner Martin, 33, got their prized pet from an animal adoption centre who took him in an unwanted pet.

She said: “He’s playful, really friendly, and he doesn’t mind my three-year-old crawling all over him. He’s like a small dog really. He has the run of the house and at night he goes in a dog’s crate. It’s a Labrador-sized cage. When he thumps on the floor its incredibly loud – you can hear it echoing around the house.”

On the night of the burglary Toby stomped his five-inch long feet so loudly on the plastic floor of his crate that he managed to wake Kimberley up.

She said: “The rabbit had obviously seen the burglar when he went into the kitchen. I heard him thump five times on the bottom of his cage and I woke up, sat up, then turned over and went back to sleep. As I’ve done that the bed springs have made a loud creaking sound, so the guy has probably heard movement and made a run for it.”

Although the thief managed to take some valuables Kimberley fears the break-in could have been even worse had it not been for Toby.

She added: “If he hadn’t been scared off he could have come upstairs looking for things. My daughter was asleep up there – it could have been really dangerous. Toby has done the job of a guard dog. We’re so proud of him we’ve rewarded him with a new tunnel to play with. It’s a cat’s tunnel obviously because he needs a big one.”

http://www.telegraph.co.uk/news/newstopics/howaboutthat/9873002/Giant-rabbit-scares-burglar-out-of-family-home.html

hunry

Over the last half decade, it has become increasingly clear that the normal gastrointestinal (GI) bacteria play a variety of very important roles in the biology of human and animals. Now Vic Norris of the University of Rouen, France, and coauthors propose yet another role for GI bacteria: that they exert some control over their hosts’ appetites. Their review was published online ahead of print in the Journal of Bacteriology.

This hypothesis is based in large part on observations of the number of roles bacteria are already known to play in host biology, as well as their relationship to the host system. “Bacteria both recognize and synthesize neuroendocrine hormones,” Norris et al. write. “This has led to the hypothesis that microbes within the gut comprise a community that forms a microbial organ interfacing with the mammalian nervous system that innervates the gastrointestinal tract.” (That nervous system innervating the GI tract is called the “enteric nervous system.” It contains roughly half a billion neurons, compared with 85 billion neurons in the central nervous system.)

“The gut microbiota respond both to both the nutrients consumed by their hosts and to the state of their hosts as signaled by various hormones,” write Norris et al. That communication presumably goes both ways: they also generate compounds that are used for signaling within the human system, “including neurotransmitters such as GABA, amino acids such as tyrosine and tryptophan — which can be converted into the mood-determining molecules, dopamine and serotonin” — and much else, says Norris.

Furthermore, it is becoming increasingly clear that gut bacteria may play a role in diseases such as cancer, metabolic syndrome, and thyroid disease, through their influence on host signaling pathways. They may even influence mood disorders, according to recent, pioneering studies, via actions on dopamine and peptides involved in appetite. The gut bacterium, Campilobacter jejuni, has been implicated in the induction of anxiety in mice, says Norris.

But do the gut flora in fact use their abilities to influence choice of food? The investigators propose a variety of experiments that could help answer this question, including epidemiological studies, and “experiments correlating the presence of particular bacterial metabolites with images of the activity of regions of the brain associated with appetite and pleasure.”

1.V. Norris, F. Molina, A. T. Gewirtz. Hypothesis: bacteria control host appetites. Journal of Bacteriology, 2012; DOI: 10.1128/JB.01384-12

http://www.sciencedaily.com/releases/2012/12/121219142301.htm

sn-sleep

Hitting the wall in the middle of a busy work day is nothing unusual, and a caffeine jolt is all it takes to snap most of us back into action. But people with certain sleep disorders battle a powerful urge to doze throughout the day, even after sleeping 10 hours or more at night. For them, caffeine doesn’t touch the problem, and more potent prescription stimulants aren’t much better. Now, a study with a small group of patients suggests that their condition may have a surprising source: a naturally occurring compound that works on the brain much like the key ingredients in chill pills such as Valium and Xanax.

The condition is known as primary hypersomnia, and it differs from the better known sleep disorder narcolepsy in that patients tend to have more persistent daytime sleepiness instead of sudden “sleep attacks.” The unknown cause and lack of treatment for primary hypersomnia has long frustrated David Rye, a neurologist at Emory University in Atlanta. “A third of our patients are on disability,” he says, “and these are 20- and 30-year-old people.”

Rye and colleagues began the new study with a hunch about what was going on. Several drugs used to treat insomnia promote sleep by targeting receptors for GABA, a neurotransmitter that dampens neural activity. Rye hypothesized that his hypersomnia patients might have some unknown compound in their brains that does something similar, enhancing the activity of so-called GABAA receptors. To try to find this mystery compound, he and his colleagues performed spinal taps on 32 hypersomnia patients and collected cerebrospinal fluid (CSF), the liquid that bathes and insulates the brain and spinal cord. Then they added the patients’ CSF to cells genetically engineered to produce GABAA receptors, and looked for tiny electric currents that would indicate that the receptors had been activated.

In that first pass, nothing happened. However, when the researchers added the CSF and a bit of GABA to the cells, they saw an electrical response that was nearly twice as big as that caused by GABA alone. All of this suggests that the patients’ CSF doesn’t activate GABAA receptors directly, but it does make the receptors almost twice as sensitive to GABA, the researchers report today in Science Translational Medicine. This effect is similar to that of drugs called benzodiazepines, the active ingredients in antianxiety drugs such as Valium. It did not occur when the researchers treated the cells with CSF from people with normal sleep patterns.

Follow-up experiments suggested that the soporific compound in the patients’ CSF is a peptide or small protein, presumably made by the brain, but otherwise its identity remains a mystery.

The idea that endogenous benzodiazepinelike compounds could cause hypersomnia was proposed in the early 1990s by Elio Lugaresi, a pioneering Italian sleep clinician, says Clifford Saper, a neuroscientist at Harvard Medical School in Boston. But several of Lugaresi’s patients later turned out to be taking benzodiazepines, which undermined his argument, and the idea fell out of favor. Saper says the new work makes a “pretty strong case.”

Based on these results, Rye and his colleagues designed a pilot study with seven patients using a drug called flumazenil, which counteracts benzodiazepines and is often used to treat people who overdose on those drugs. After an injection of flumazenil, the patients improved to near-normal levels on several measures of alertness and vigilance, the researchers report. Rye says these effects lasted up to a couple hours.

In hopes of longer-lasting benefits, the researchers persuaded the pharmaceutical company Hoffmann-La Roche, which makes the drug, to donate a powdered form that can be incorporated into dissolvable tablets taken under the tongue and a cream applied to the skin. One 30-something patient has been taking these formulations for 4 years and has improved dramatically, the researchers report in the paper. She has resumed her career as an attorney, from which her hypersomnia had forced her to take a leave of absence.

The findings are “certainly provocative,” Saper says, although they’ll have to be replicated in a larger, double-blind trial to be truly convincing.

Even so, says Phyllis Zee, a neurologist at Northwestern University in Evanston, Illinois: “This gives us a new window into thinking about treatments” for primary hypersomnia. “These patients don’t respond well to stimulants,” Zee says, so a better strategy may be to inhibit the sleep-promoting effects of GABA—or as Rye puts it, releasing the parking brake instead of pressing the accelerator.

The next steps are clear, Rye says: Identify the mystery compound, figure out a faster way to detect it, and conduct a larger clinical trial to test the benefits of flumazenil. However, the researchers first need someone to fund such a study. So far, Rye says, they’ve gotten no takers.

http://news.sciencemag.org/sciencenow/2012/11/putting-themselves-to-sleep.html

sn-autism

 

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.

The current study already looks interesting to some. “It’s enough to make me think about trying it in a few of my autism patients who haven’t responded to other interventions,” says Randi Hagerman, a pediatrician who studies neurodevelopmental disorders at the University of California, Davis. Social interactions tend to be reinforcing, Hagerman adds, so getting an autistic child to start interacting more can have a positive effect on subsequent brain development.

Other drugs have recently shown promise for autism. In September, Hagerman and colleagues reported that arbaclofen, a drug that stimulates a type of GABA receptor, reduced social avoidance in people with fragile X syndrome, a genetic disorder that shares many features with autism. Many researchers are also hopeful about clinical trials under way with drugs that block certain receptors for glutamate, the main neurotransmitter in the brain that excites neural activity. Results from those trials should come out next year.

All of this work, including the new study, suggests that drugs that reduce neural excitation by blocking glutamate or enhance inhibition by boosting GABA may be helpful for treating autism, says Elizabeth Berry-Kravis, a pediatric neurologist at Rush University in Chicago, Illinois, and a collaborator on the recent arbaclofen study. “There seems to be this imbalance between excitation and inhibition in people with autism.”

That’s a potentially game-changing insight. Now doctors can only prescribe drugs that treat individual symptoms of autism rather than the underlying cause of the disorder, Berry-Kravis says. Doctors often prescribe antipsychotic drugs to reduce irritability, for example, but those drugs don’t address the social and communication problems at the heart of the disorder. “It’s exciting that now we’re thinking about the underlying mechanisms and treating those.”

http://news.sciencemag.org/sciencenow/2012/12/diuretic-drug-offers-latest-hope.html