“Brain metabolism in vitro” and those sour energy substrates

Brain metabolism,Energy Substrates,Excitatory GABA,Glucose,Ketone bodies,Lactate,Pyruvate — Tags: , — 10:31 am

Part 2. Energy substrates: too sour?
Part 3. Let the neurons breathe!
This paper suggests that the developmental switch in the reversal potential for gamma-aminobutyric acid (GABA) is regulated by different energy sources

This paper suggests that the developmental switch in the reversal potential for gamma-aminobutyric acid (GABA) is regulated by different energy sources

An evaluation of our article (1) appeared in the “Faculty of 1000 postpublication peer reviews” the conclusion being:

The findings of Rheims et al. have a potentially major impact on our understanding of GABAergic function during development, bringing back an element of inhibition in developing neuronal networks that appeared to rely entirely on excitatory connections (2).

This article (1) along with the article (3) later became an indirect subject of another evaluation (4) although formally, the evaluation concerned a different paper (5), which has been commended because (the author’s words):

“It settles an important issue related to brain metabolism in vitro and the role of acidification in brain patterns.”

The acidification issue doesn’t seem to be resolved either in 5 nor in 4, so a comment to the evaluation appeared in May 2011,  stating among other things the following:

We showed that inhibition of spontaneous network activity in neonatal hippocampal slices by energy substrates is not correlated with intracellular acidification (7) and that they work altering intrinsic features of energy metabolism namely NAD(P)H and oxygen utilization (8).

Another data challenged in 5 is whether lactate as efficient as an energy substrate: “Lactate is not an efficient replacement for glucose” wrote Dr Ben-Ari and Y. Zilberter in his comment referred to the paper 8 titled “Lactate effectively covers energy demands during neuronal network activity in neonatal hippocampal slices” and the work of Wyss et al. (9) titled “In Vivo Evidence for Lactate as a Neuronal Energy Source”.

References

1. Rheims S, Holmgren CD, Chazal G, Mulder J, Harkany T, Zilberter T, Zilberter Y. (2009) J Neurochem.  Aug;110(4):1330-8. Epub 2009 Jun 22. (on Brain Fuels)

2. Scimemi A, Diamond J: 2009. F1000.com/1166168

3. Holmgren CD, Mukhtarov M, Malkov AE, Popova IY, Bregestovski P, Zilberter Y. (2010) J Neurochem. Feb;112(4):900-12. Epub 2009 Nov 24. (on Brain Fuels)

4. Ben-Ari Y: 2011. F1000.com/6913961

5. Ruusuvuori E, Kirilkin I, Pandya N, Kaila K (2010) J Neurosci.  Nov 17; 30(46):15638-42

6. Zilberter Y, Zilberter T, Bregestovski P. (2010) Trends Pharmacol Sci., 31(9):394-401 (on Brain Fuels)

7. Mukhtarov, M., Ivanov, A., Zilberter, Y., and Bregestovski, P. (2011) J Neurochem 116, 316-321

8. Ivanov A, Mukhtarov M, Bregestovski P and Zilberter Y (2011) Front. Neuroenerg. 3:2.

9. Wyss M, Jolivet R, Buck A, Magistretti P, and Weber B. (2011)  J Neuroscience, 31(20):7477-7485

The metabolic rate of plasma-borne lactate is a function of brain lactate concentration

Astrocyte–neuron lactate shuttle,Lactate — Tags: , — 5:07 am

In the Journal club section of the Journal of Neuroscience (written exclusively by graduate students or postdoctoral fellows), a review by C. Figley from Johns Hopkins University and Kennedy Krieger Institute, Baltimore, Maryland was recently published, concluding: “…neurons are capable of transporting and metabolizing large quantities of lactate in vivo” and “…cultured neurons might preferentially oxidize lactate as their primary metabolic substrate”

Chase R. Figley. Human Brain: Implications for the Astrocyte-Neuron Lactate Shuttle Hypothesis. J Neuroscience, 2011, 31(13): 4768-4770; doi: 10.1523/​JNEUROSCI.6612-10.2011




Neuronal activity in vitro and the in vivo reality

Energy Homeostasis,Energy Substrates,Excitatory GABA,Methodology — Tags: , , , , , , , , , — 1:15 pm
In the brain, neuronal electrical activity and intricate metabolic energy provisions are closely related. Although both functions have been painstakingly researched by electrophysiologists and biochemists, insufficient interaction between the two domains leads to difficulty in extrapolating the properties observed in the in vitro studies to the properties of the whole in vivo brain. In this paper, we hope to clarify the relationships between neuronal energy status and neuronal electrical function.

“A man with his head is something much more then a man’s body plus his separate head” – J. Miller (1965)

Whole is equal to more than the sum of its parts (on some interdisciplinary methodological problems)

In the history of life sciences, perhaps beginning with Aristotle’s time, reductionism prevailed leaving the opposite philosophical approach, holism, outside scientific paradigm. Reductionism and reductionists are concerned with at least two dominant themes: a) the interactions between different domains of knowledge; b) the place of a part in the whole (1). (more…)

Pyruvate protects neurons against A-beta peptides characteristic for Alzheimer’s

Neuroprotectors,Pyruvate — Tags: , , , , , — 8:26 am

Pyruvate is one of major energy carriers in the brain, it is shown to be protective against damaging consequences of neurotoxins, such as hydrogen peroxide, glutamate, zinc, and copper/cysteine (1). Pyruvate plus another energy substrate, malate, in addition to standard glucose concentrations, protects embryonic neurons in the brain region such as hippocampus and cortex against glutamate excitotoxicity (2). These pyruvate and malate effects promoting neuronal survival were preferential over over glucose suggested that glucose-derived pyruvate from glucose may be limited in neurons studied in vitro, especially under conditions of elevated energy demands. neurons.

Supplementation of glucose-containing culture media with energy substrates, pyruvate plus malate (P/M), protected rat primary neurons from degeneration and death caused by A-beta peptides characteristic for Alzheimer’s disease (3).

Source: Pyruvate Protection Against -Amyloid-Induced Neuronal Death: Role of Mitochondrial Redox State. Gema Alvarez, Milagros Ramos, Francisca Ruiz, Jorgina Satrustegui, and Elena Bogonez. Journal of Neuroscience Research 73:260-269 (2003)

Citations from the source:

  1. Eimerl and Schramm 1995; Desagher et al., 1997; Ruiz et al., 1998; Sheline et al., 2000; Wang and Cynader, 2001
  2. Ruiz et al., 1998
  3. Alvarez et al., 2003

Additional information

Ivanov et al. (2011) supplemented glucose with 5 mM pyruvate in ACSF. Pyruvate induced a strong increase in the NAD(P)H oxidation phase and oxygen consumption during neuronal stimulation suggesting that pyruvate enhances aerobic energy metabolism and synaptic integrity. Effects of pyruvate in the same concentration on normalization of on GABA reversal potential first shown by Y. Zilberter’s group (Holmgren et al., 2010) has been confirmed by Tyzio et al. (2011) although the authors, for some reason measuring pyruvate contents in the blood, not ECF, arrived at the conclusion that the concentration was non-physiological  (see discussion here)

References

  • Ivanov A, Mukhtarov M, Bregestovski P and Zilberter Y (2011). Lactate effectively covers energy demands during neuronal network activity in neonatal hippocampal slices. Front. Neuroenerg. 3:2.
  • Tyzio R, Allene C, Nardou R, Picardo M, Yamamoto S, Sivakumaran S, Caiati MD, Rheims S, Minlebaev M, Milh M, Ferre P, Khazipov R, Romette J-L, Lorquin J, Cossart R, Khalilov I, Nehlig A, Cherubini E, Ben-Ari Y. (2011) Depolarizing Actions of GABA in Immature Neurons Depend Neither on Ketone Bodies Nor on Pyruvate. pp 34-45.

Maturity levels determine energy substrate use

Brain metabolism,Glucose,Ketone bodies — Tags: , , , — 8:05 am

The newborns are not created equal.

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