“Sweet slices are fine” – really?

Neuroscience FAQ, Q&A — 7:08 am

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Question: Hi Tanya, I’ve read your recent entry to the blog brainfuels.com/2011/05/sweet-and-sour-recipes… and am lookin’ forward to reading the  rest in the series. My question is, is the “GABA scandal” finally resolved? Asking because so far, you haven’t mentioned this aspect.

Than you, Ingrid

Answer: Hi Ingrid,

The bottom line might look like this: the authors of the three articles rebutting results of Dr Yu. Zilberter’s group  (all references are in the post you’ve mentioned ) did not indeed reproduce SOME of the results – but then they did not try to reproduce the experimental conditions, so how are we supposed to compare? On the other hand, Ivanov et al., checked what’s going on in the experimental conditions used by their opponents and were able to show that the differences are easily explainable. The parts 2 to 4 of the “Sweet and sour recipes for the brain” will discuss the differences one by one, from acidification to oxygenation to slice handling.

Importantly, two of the three opponent’s articles did reproduce results of Yu. Zilberter with coworkers (concerning pyruvate and lactate) however interpreting them in the way that will also be elucidated in the series and that has been already discussed in our review article (Zilberter et al., 2010) by the time when the interpretation was published, e.g., Tyzio et al., 2011.

Hope it helps,

Tanya Zilberter

Placebo: a medicine created by the mind

The word placebo initially meant “I will please”: “Placebo Domino in regione vivorum” (“I shall please the Lord in the land of the living,” referring to the Latin translation of the Bible by Jerome, Psalms, Septuagint, 1). Practically, it means something like sugar pills known to have effects similar to a real medicine while being biologically inactive. The placebo effect is so strong that it’s a standard to exclude its influence when a drug is being tested. Not only patients but also their physicians must be unaware of what kind of pills is given to whom, a procedure called double-blind control.

Until mid-20th century, placebo used to be a common practice although it was considered genuinely ineffective from therapeutic standpoint. The belief was that intelligent patients were less prone to benefit from it (2). Currently, there’s a solid body of evidence that in many cases placebo effect closely minicks that of pharmacologically active drugs, for instance, Ramipril versus placebo (3) reduced the rates of death from:

  • cardiovascular causes – 6.1 % vs 8.1 %
  • myocardial infarction – 9.9 % vs. 12.3 %
  • stroke 3.4 % vs. 4.9 %
  • complications related to diabetes 6.4 % vs. 7.6 %

Interestingly, in children, effects of placebo is 2-fold higher than in adults (4).

In the article “Placebo-Induced Changes in fMRI in the Anticipation and Experience of Pain” (5) the authors reported data supporting the hypothesis that placebo works via decrease in neuronal activity in brain regions sensitive to pain. They concluded: These findings provide strong refutation of the conjecture that placebo responses reflect nothing more than report bias (6)”

A very good video-summary of placebo effect: The Strange Powers of the Placebo Effect

Sources

1. J R Soc Med. 2000 April; 93(4): 213–214.
2. J R Soc Med. 1999 October; 92(10): 511–515.
3. N Engl J Med. 2000 Jan 20;342(3):145-53.
4. PLoS Med 5(8): e166. doi:10.1371/journal.pmed.0050166
5. Science 20 February 2004:
Vol. 303 no. 5661 pp. 1162-1167
6. N. Engl. J. Med. 344, 1594 (2001).

Neuroprotective effects of Coenzyme Q10

Related: Is Q10 a fitness-enhancing or an anti-aging supplement in the long run?

“Several clinical trials of CoQ10 have been performed in Parkinson’s disease and atypical Parkinson’s syndromes, Huntington’s disease, Alzheimer disease, Friedreich’s ataxia, and amyotrophic lateral sclerosis, with equivocal findings. CoQ10 is widely available in multiple formulations and is very well tolerated with minimal adverse effects, making it an attractive potential therapy.”
Meredith Spindler, M Flint Beal, and Claire Henchcliffe. Coenzyme Q10 effects in neurodegenerative disease. Neuropsychiatr Dis Treat. 2009; 5: 597–610
“There is ample evidence showing involvement of mitochondrial dysfunction in the pathogenesis of neurodegenerative disorders, therefore, one would predict that agents that alleviate mitochondrial dysfunction could be beneficial and exert neuroprotective effects. Several bioenergetic agents that improve mitochondrial function including creatine, coenzyme Q10 (CoQ10), nicotinamide, riboflavin and lipoic acid are being tested for their neuroprotective efficacy in neurodegenerative disorders. Among them, creatine and CoQ10 are in clinical trials for PD, HD and AD.”
Rajnish K. Chaturvedi and M. Flint Beal. Mitochondrial approaches for neuroprotection. Ann N Y Acad Sci. 2008 December; 1147: 395–412
“…combination therapy using CoQ10 and creatine may be useful in the treatment of neurodegenerative diseases such as Parkinson’s disease and HD.”
Lichuan Yang  et al., Combination therapy with Coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson’s and Huntington’s Diseases. J Neurochemistry, 109, 5, 1427–1439, 2009
“…a synthetic analog of CoQ10, idebenone, has been investigated in clinical trials for its ability to inhibit lipid peroxidation. Although several smaller studies reported beneficial effects on memory and attention after several months of treatment, a larger study reported no effect in slowing disease progression.”
Magali Dumont, M. Flint Beal. Neuroprotective strategies involving ROS in Alzheimer disease. Free Radical Biology and Medicine, 2011, online ahead of print
“These data demonstrate that in addition to reducing intracellular deposition of A-beta, CoQ10 can also reduce plaque pathology. Our study further supports the use
of CoQ10 as a therapeutic candidate for AD.”
Xifei Yang et al., Coenzyme Q10 Reduces β-Amyloid Plaque in an APP/PS1
Transgenic Mouse Model of Alzheimer’s Disease. Mol Neurosci (2010) 41:110–113
Abbreviations

PD: Parkinson’s disease;
HD: Huntington’s disease;
AD: Alzheimer’s disease;
A-beta – beta-Amyloid peptide
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