Brain Physiology, Cognition and Consciousness: notice board entry
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Glutamate Uptake in a Model of Absence Epilepsy
- Posted by:
- Alfredo Pereira Jr (group admin)
- Date:
- 30 August 2007
- Comments:
- 1 comment
Dear All:
Absence Epilepsy is a central field for Consciousness research, since there is basically a loss of consciousness during a seizure (in other kinds of Epilepsy, there are severe motor effects together with the loss of consciousness).
A new paper confirms the role of glutamate in absence epilepsy (below; thanks to Marcelo Mercante for calling my attention to this publication).
Best Regards,
Alfredo
http://www.biomedcentral.com/1471-2202/8/69/abstract
Research article
.
Glutamatergic alterations in cortex of genetic absence epilepsy rats
Monique Touret , Sandrine Parrot , Luc Denoroy , Marie-Francoise
Belin and Marianne Didier-Bazes
BMC Neuroscience 2007, 8:69 doi:10.1186/1471-2202-8-69
Published 29 August 2007
Abstract (provisional)
The complete article is available as a provisional PDF. The fully
formatted PDF and HTML versions are in production.
Background
In Absence Epilepsy, the neuronal hyper-excitation and hyper-
synchronization which induce spike and wave discharges in a cortico-
thalamic loop, are suspected of involving an imbalance between GABA
and glutamate neurotransmission. In order to elucidate the role
played by glutamate in the outcome of disease, we determined
cortical and thalamic extracellular glutamate as well as GABA
concentrations. For that purpose, we used an in vivo quantitative
microdialysis approach (no-net-flux method) in an animal model of
Absence Epilepsy (GAERS). In addition by infusing labelled glutamate
through the microdialysis probe, we studied in vivo glutamate uptake
in cortex and thalamus of GAERS and non-epileptic control (NEC)
rats. Expression of vesicular glutamate transporters (VGLUT1,
VGLUT2) and synaptophysin a synaptic component, were also considered
in the thalamo-cortical loop.
Results
While the values of GABA and glutamate extra-cellular concentrations
in cortex and thalamus were not significantly different between
GAERS and NEC rats, the cortical glutamate uptake was found
significantly decreased in unrestrained awake GAERS. Expressions of
vesicular glutamate transporter VGLUT2 and synaptophysin were
increased in cortex of GAERS compared to NEC rats, whereas no
changes were observed in thalamus.
Conclusion
The specific decrease in glutamate uptake in cortex of GAERS linked
to synaptic changes, suggested an impairment of glutamatergic
terminal network.These data emphasize the idea of alteration in
glutamatergic neurotransmission, in cortex which could contribute to
hyper-excitability in Absence Epilepsy.
Hello All:
The notice below leads me to speculate that glutamate levels in the brain are affected by the ingestion of carbohidrates (as far as the blood-brain barrier permits, of course!).
Alfredo
Low carb diet curbs epileptic fits in children· Trial shows seizures can be cut by more than 50%
· Scientists still unsure how ketogenic regime works
James Randerson, science correspondent
The Guardian, Saturday May 3 2008 Article historyAbout this articleClose This article appeared in the Guardian on Saturday May 03 2008 on p21 of the UK news section. It was last updated at 00:09 on May 03 2008. Giving children with epilepsy a special low carb diet reduces the number of seizures they experience by 75% compared with children on a normal diet, according to a study carried out at Great Ormond Street Hospital.
Previous studies have suggested that the food regime, which is similar to the Atkins diet, is effective at curbing epilepsy but this is the first gold standard clinical trial to prove that it works.
“When she went on the diet within days she was just so much calmer,” said Rachel Farrand of Redhill, Surrey, whose six-year-old daughter, Ella Strutton, was part of the trial. “It’s just had a really big impact on her behaviour and her learning.”
Ella developed epilepsy after contracting meningitis when she was one. She is now profoundly deaf, has severe learning difficulties and before taking part in the trial she was suffering up to 12 seizures a day. “It made it very hard for her to learn because she couldn’t concentrate at all,” said Farrand. “She was a complete and absolute whirlwind. She couldn’t settle for anything even for a minute.” After starting the diet she was seizure-free for six months and now no longer needs to take anti-epilepsy medication.
About one in 200 children are affected by epilepsy, which can often be controlled with regular drugs.
Professor Helen Cross at the Institute of Child Health at University College London and her colleagues recruited 145 children – including Ella – aged between two and 16 who all had severe epilepsy. Half were randomly assigned to a ketogenic diet, which involves eating no carbohydrate and no more than the minimum dietary requirement of protein. Fat is permitted. The other half ate a normal diet. Forty-two children were not included in the final analysis for a variety of reasons.
The team found that the number of seizures per day in the ketogenic diet group dropped to 62% of the level before the change, while the control group’s seizures increased by 37%. Twenty-eight children in the diet group had a more than 50% reduction in their seizures compared with four in the control group. The results are reported in the journal Lancet Neurology. Cross said it was important to have confirmed that the ketogenic diet is effective by the gold standard scientific method. “At the present time it is a treatment that is really reserved for the really intractable. It’s available in only a minimal number of centres,” she said.
She added that parents should only consider trying the diet after consultation with a doctor and dietician. “Children are growing and need the right number of calories… so it does need to be monitored and calculated individually,” she said.
As yet, scientists are unsure what changes occur with the diet, although it is possible that it prompts a physiological shift that affects the brain. “There’s all sorts of theories from a basic science point of view that have been put forward, but we haven’t got the exact reason why it works,” said Cross.
The study is important because it is the first time the question of whether the diet works has been tackled using a randomised clinically controlled trial – widely acknowledged as the best method for assessing whether medical interventions are effective.