Neuronal activity in vitro and the in vivo reality

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…)

Barriers and fluids that connect and divide blood, brain, and neurons

Methodology — Tags: , , , — 11:07 am

BRAIN EXTRACELLULAR FLUID

Read also: The History of Artificial Cerebrospinal Fluid (ACSF)

The brain is protected by a rigid bony case so it cannot expand in the case of fluid imbalance. Because of that, the brain needs to tightly control the flux across the cerebral capillaries and this line of defence or restriction of chemical communications between blood and brain, called blood-brain barrier, was introduced by the work of Erhlich et al., in nineteenth century and the classic experiment of Goldman confirmed the concept of the blood-brain barrier (reviewed in 1). (more…)

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

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.
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