Frontiers in Neuroenergetics

We present the perspective that lactate is a volume transmitter of cellular signals in brain that acutely and chronically regulate the energy metabolism of large neuronal ensembles. From this perspective, we interpret recent evidence to mean that lactate transmission serves the maintenance of network metabolism by two different mechanisms, one by regulating the formation of cAMP via the lactate receptor GPR81, the other by adjusting the NADH/NAD(+) redox ratios, both linked to the maintenance of brain energy turnover and possibly cerebral blood flow...

Glycogen is a complex glucose polymer found in a variety of tissues, including brain, where it is localized primarily in astrocytes. The small quantity found in brain compared to e.g., liver has led to the understanding that brain glycogen is merely used during hypoglycemia or ischemia. In this review evidence is brought forward highlighting what has been an emerging understanding in brain energy metabolism: that glycogen is more than just a convenient way to store energy for use in emergencies-it is a highly dynamic molecule with versatile implications in brain function, i...

Existing current based models that capture spike activity, though useful in studying information processing capabilities of neurons, fail to throw light on their internal functioning. It is imperative to develop a model that captures the spike train of a neuron as a function of its intracellular parameters for non-invasive diagnosis of diseased neurons. This is the first ever article to present such an integrated model that quantifies the inter-dependency between spike activity and intracellular energetics...

No abstract text is available yet for this article.

Flickering light dilates retinal arterioles and increases retinal blood flow, a response termed functional hyperemia. This response is diminished in diabetic patients even before the appearance of overt clinical retinopathy. The loss of functional hyperemia could deprive retinal neurons of oxygen and nutrients, possibly exacerbating the development of diabetic retinopathy. We have tested whether inhibiting inducible nitric oxide synthase (iNOS) reverses the loss of functional hyperemia in diabetic rat retinas in vivo...

No abstract text is available yet for this article.

The interactive vasculo-neuro-glial system controlling energy supply in the brain is absent in vitro where energy provision is determined by experimental conditions. Despite the fact that neuronal activity is extremely energy demanding, little has been reported on the state of energy metabolism in submerged brain slices. Without this information, the arbitrarily chosen oxygenation and metabolic provisions make questionable the efficient oxidative metabolism in slices. We show that in mouse hippocampal slices (postnatal day 19-44), evoked neuronal discharges, spontaneous network activity (initiated by 4-aminopyridine), and synaptic stimulation-induced NAD(P)H autofluorescence depend strongly on the oxygen availability...

No abstract text is available yet for this article.

Accumulating evidence suggests that different energy metabolites play a role not only in neuronal but also in glial signaling. Recently, astroglial Ca(2+) transients evoked by the major citric acid cycle metabolite succinate (SUC) and gamma-hydroxybutyrate (GHB) that enters the citric acid cycle via SUC have been described in the brain reward area, the nucleus accumbens (NAc). Cells responding to SUC by Ca(2+) transient constitute a subset of ATP-responsive astrocytes that are activated in a neuron-independent way...

No abstract text is available yet for this article.

Metabolic models have been used to elucidate important aspects of brain metabolism in recent years. This work applies for the first time the concept of isotopic transient 13C metabolic flux analysis (MFA) to estimate intracellular fluxes in primary cultures of astrocytes. This methodology comprehensively explores the information provided by 13C labeling time-courses of intracellular metabolites after administration of a 13C-labeled substrate. Cells were incubated with medium containing [1-13C]glucose for 24 h and samples of cell supernatant and extracts collected at different time points were then analyzed by mass spectrometry and/or high performance liquid chromatography...

Cerebral metabolism is compartmentalized between neurons and glia. Although glial glycolysis is thought to largely sustain the energetic requirements of neurotransmission while oxidative metabolism takes place mainly in neurons, this hypothesis is matter of debate. The compartmentalization of cerebral metabolic fluxes can be determined by (13)C nuclear magnetic resonance (NMR) spectroscopy upon infusion of (13)C-enriched compounds, especially glucose. Rats under light α-chloralose anesthesia were infused with [1,6-(13)C]glucose and (13)C enrichment in the brain metabolites was measured by (13)C NMR spectroscopy with high sensitivity and spectral resolution at 14...

No abstract text is available yet for this article.

Although numerous experimental data indicate that lactate is efficiently used for energy by the mature brain, the direct measurements of energy metabolism parameters during neuronal network activity in early postnatal development have not been performed. Therefore, the role of lactate in the energy metabolism of neurons at this age remains unclear. In this study, we monitored field potentials and contents of oxygen and NAD(P)H in correlation with oxidative metabolism during intense network activity in the CA1 hippocampal region of neonatal brain slices...

The neurovascular system may be viewed as a distributed nervous system within the brain. It transforms local neuronal activity into a change in the tone of smooth muscle that lines the walls of arterioles and microvessels. We review the current state of neurovascular coupling, with an emphasis on signaling molecules that convey information from neurons to neighboring vessels. At the level of neocortex, this coupling is mediated by: (i) a likely direct interaction with inhibitory neurons, (ii) indirect interaction, via astrocytes, with excitatory neurons, and (iii) fiber tracts from subcortical layers...

The current understanding of fMRI, regarding its vascular origins, is based on numerous assumptions and theoretical modeling, but little experimental validation exists to support or challenge these models. The known functional properties of cerebral vasculature are limited mainly to the large pial surface and the small capillary level vessels. However, a significant lack of knowledge exists regarding the cluster of intermediate-sized vessels, mainly the intracortical, connecting these two groups of vessels and where, arguably, key blood flow regulation takes place...

Microglia are immune cells within the central nervous system. In brain-developing tumors, gliomas are able to silence the defense and immune functions of microglia, a phenomenon which strongly contributes to tumor progression and treatment resistance. Being activated and highly motile, microglia infiltrate tumors and secrete macrophagic chemoattractant factors. Thereafter, the tumor cells shut down their immune properties and stimulate the microglia to release tumor growth-promoting factors. The result of such modulation is that a kind of symbiosis occurs between microglia and tumor cells, in favor of tumor growth...

Assessing neuronal activity by non-invasive functional brain imaging techniques which are based on the hemodynamic response depends totally on the physiological cascade of metabolism and blood flow. At present, functional brain imaging with near infrared spectroscopy (NIRS) or BOLD-fMRI is widely used in cognitive neuroscience in healthy subjects where neurovascular coupling and cerebrovascular reactivity can be assumed to be intact. Local activation studies as well as studies investigating functional connectivity between brain regions of the resting brain provide a rapidly increasing body of knowledge on brain function in humans and animals...

Laser speckle flowmetry (LSF) was initially developed to measure blood flow in the retina. More recently, its primary application has been to image baseline blood flow and activity-dependent changes in blood flow in the brain. We now describe experiments in the rat retina in which LSF was used in conjunction with confocal microscopy to monitor light-evoked changes in blood flow in retinal vessels. This dual imaging technique permitted us to stimulate retinal photoreceptors and measure vessel diameter with confocal microscopy while simultaneously monitoring blood flow with LSF...

Astrocytes are organized as networks of communicating cells due to their high expression level of connexins, the molecular constituents of gap junction channels. Based on their permeability properties for ions and small signaling molecules such astroglial wiring interferes with neuronal activity and survival. In this paper, I identify and discuss which future technical and conceptual progress or advances should be achieved in order to better understand how neuroglial networking contributes to brain functions and dysfunctions...