scholarly journals Lactate-mediated glia-neuronal signalling in the mammalian brain

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
F. Tang ◽  
S. Lane ◽  
A. Korsak ◽  
J. F. R. Paton ◽  
A. V. Gourine ◽  
...  

Abstract Astrocytes produce and release L-lactate as a potential source of energy for neurons. Here we present evidence that L-lactate, independently of its caloric value, serves as an astrocytic signalling molecule in the locus coeruleus (LC). The LC is the principal source of norepinephrine to the frontal brain and thus one of the most influential modulatory centers of the brain. Optogenetically activated astrocytes release L-lactate, which excites LC neurons and triggers release of norepinephrine. Exogenous L-lactate within the physiologically relevant concentration range mimics these effects. L-lactate effects are concentration-dependent, stereo-selective, independent of L-lactate uptake into neurons and involve a cAMP-mediated step. In vivo injections of L-lactate in the LC evokes arousal similar to the excitatory transmitter, L-glutamate. Our results imply the existence of an unknown receptor for this ‘glio-transmitter’.

2018 ◽  
Vol 47 (1) ◽  
pp. 302-315 ◽  
Author(s):  
Shiying Sheng ◽  
Jingzhong Huang ◽  
Yi Ren ◽  
Feng Zhi ◽  
Xuansong Tian ◽  
...  

The delta-opioid receptor (DOR) is one of three classic opioid receptors in the opioid system. It was traditionally thought to be primarily involved in modulating the transmission of messages along pain signaling pathway. Although there were scattered studies on its other neural functions, inconsistent results and contradicting conclusions were found in past literatures, especially in terms of DOR’s role in a hypoxic/ischemic brain. Taking inspiration from the finding that the turtle brain exhibits a higher DOR density and greater tolerance to hypoxic/ischemic insult than the mammalian brain, we clarified DOR’s specific role in the brain against hypoxic/ischemic injury and reconciled previous controversies in this aspect. Our serial studies have strongly demonstrated that DOR is a unique neuroprotector against hypoxic/ischemic injury in the brain, which has been well confirmed in current research. Moreover, mechanistic studies have shown that during acute phases of hypoxic/ischemic stress, DOR protects the neurons mainly by the stabilization of ionic homeostasis, inhibition of excitatory transmitter release, and attenuation of disrupted neuronal transmission. During prolonged hypoxia/ischemia, however, DOR neuroprotection involves a variety of signaling pathways. More recently, our data suggest that DOR may display its neuroprotective role via the BDNF-TrkB pathway. This review concisely summarizes the progress in this field.


Science ◽  
2011 ◽  
Vol 333 (6047) ◽  
pp. 1262-1266 ◽  
Author(s):  
Xiaoke Chen ◽  
Mariano Gabitto ◽  
Yueqing Peng ◽  
Nicholas J. P. Ryba ◽  
Charles S. Zuker

The taste system is one of our fundamental senses, responsible for detecting and responding to sweet, bitter, umami, salty, and sour stimuli. In the tongue, the five basic tastes are mediated by separate classes of taste receptor cells each finely tuned to a single taste quality. We explored the logic of taste coding in the brain by examining how sweet, bitter, umami, and salty qualities are represented in the primary taste cortex of mice. We used in vivo two-photon calcium imaging to demonstrate topographic segregation in the functional architecture of the gustatory cortex. Each taste quality is represented in its own separate cortical field, revealing the existence of a gustotopic map in the brain. These results expose the basic logic for the central representation of taste.


2009 ◽  
Vol 29 (6) ◽  
pp. 1121-1129 ◽  
Author(s):  
Gerrit van Hall ◽  
Morten Stømstad ◽  
Peter Rasmussen ◽  
Øle Jans ◽  
Morten Zaar ◽  
...  

Lactate is a potential energy source for the brain. The aim of this study was to establish whether systemic lactate is a brain energy source. We measured in vivo cerebral lactate kinetics and oxidation rates in 6 healthy individuals at rest with and without 90 mins of intravenous lactate infusion (36 μmol per kg bw per min), and during 30mins of cycling exercise at 75% of maximal oxygen uptake while the lactate infusion continued to establish arterial lactate concentrations of 0.89 ± 0.08, 3.9 ± 0.3, and 6.9 ± 1.3 mmol/L, respectively. At rest, cerebral lactate utilization changed from a net lactate release of 0.06 ± 0.01 to an uptake of 0.16 ± 0.07 mmol/min during lactate infusion, with a concomitant decrease in the net glucose uptake. During exercise, the net cerebral lactate uptake was further increased to 0.28 ± 0.16 mmol/min. Most 13C-label from cerebral [1-13C]lactate uptake was released as 13CO2 with 100% ± 24%, 86% ± 15%, and 87% ± 30% at rest with and without lactate infusion and during exercise, respectively. The contribution of systemic lactate to cerebral energy expenditure was 8% ± 2%, 19% ± 4%, and 27% ± 4% for the respective conditions. In conclusion, systemic lactate is taken up and oxidized by the human brain and is an important substrate for the brain both under basal and hyperlactatemic conditions.


1951 ◽  
Vol 97 (409) ◽  
pp. 674-680 ◽  
Author(s):  
H. McIlwain

Effects of substances on the respiration of unstimulated portions of mammalian brain have been used in the past as aids to understanding or suggesting their actions on the brain in vivo. The present paper gives data with respect to glucose and glutamic acid, which show some of the limitations of such interpretations. It also describes the application of new experimental means of examining the metabolic effects of added substances in relation to the functional activity of the brain.


2019 ◽  
Author(s):  
Nicola Pellicciotta ◽  
Evelyn Hamilton ◽  
Jurij Kotar ◽  
Marion Faucourt ◽  
Nathalie Degehyr ◽  
...  

Motile cilia are widespread across the animal and plant kingdoms, displaying complex collective dynamics central to their physiology. Their coordination mechanism is not generally understood, with pre-vious work mainly focusing on algae and protists. We study here the synchronization of cilia beat in multiciliated cells from brain ven-tricles. The response to controlled oscillatory external flows shows that strong flows at a similar frequency to the actively beating cilia can entrain cilia oscillations. We find that the hydrodynamic forces required for this entrainment strongly depend on the number of cilia per cell. Cells with few cilia (up to five) can be entrained at flows comparable to the cilia-driven flows reported in vivo. Simulations of a minimal model of cilia interacting hydrodynamically show the same trends observed in cilia. Our results suggest that hydrody-namic forces between cilia are sufficient to be the mechanism behind the synchronization of mammalian brain cilia dynamics.Significance StatementIt is shown experimentally, and also reproducing key qualitative results in a minimal mechanistic model simulated numerically, that in the motile cilia of the brain hydrodynamic forces of the magnitude that cilia themselves can generate are sufficient to establish the coordination of dynamics which is so crucial phys-iologically. This is the first experiment of its kind on multicilated cells, the key result is the unexpected importance of cilia num-ber per cell, with cells with fewer cilia much more susceptible to external flows. This finding changes the way in which we think about the question of collective cilia beating - it is not correct to simply examine isolated cilia and draw conclusions about the behaviour of cilia assemblies in multiciliated cells.


Author(s):  
Beverly E. Maleeff ◽  
Timothy K. Hart ◽  
Stephen J. Wood ◽  
Ronald Wetzel

Alzheimer's disease is characterized post-mortem in part by abnormal extracellular neuritic plaques found in brain tissue. There appears to be a correlation between the severity of Alzheimer's dementia in vivo and the number of plaques found in particular areas of the brain. These plaques are known to be the deposition sites of fibrils of the protein β-amyloid. It is thought that if the assembly of these plaques could be inhibited, the severity of the disease would be decreased. The peptide fragment Aβ, a precursor of the p-amyloid protein, has a 40 amino acid sequence, and has been shown to be toxic to neuronal cells in culture after an aging process of several days. This toxicity corresponds to the kinetics of in vitro amyloid fibril formation. In this study, we report the biochemical and ultrastructural effects of pH and the inhibitory agent hexadecyl-N-methylpiperidinium (HMP) bromide, one of a class of ionic micellar detergents known to be capable of solubilizing hydrophobic peptides, on the in vitro assembly of the peptide fragment Aβ.


Author(s):  
Enrico D.F. Motti ◽  
Hans-Georg Imhof ◽  
Gazi M. Yasargil

Physiologists have devoted most attention in the cerebrovascular tree to the arterial side of the circulation which has been subdivided in three levels: 1) major brain arteries which keep microcirculation constant despite changes in perfusion pressure; 2) pial arteries supposed to be effectors regulating microcirculation; 3) intracerebral arteries supposed to be deprived of active cerebral blood flow regulating devices.The morphological search for microvascular effectors in the cerebrovascular bed has been elusive. The opaque substance of the brain confines in vivo investigation to the superficial pial arteries. Most morphologists had to limit their observation to the random occurrence of a favorable site in the practically two-dimensional thickness of diaphanized histological sections. It is then not surprising most investigators of the cerebral microcirculation refer to an homogeneous network of microvessels interposed between arterioles and venules.We have taken advantage of the excellent depth of focus afforded by the scanning electron microscope (SEM) to investigate corrosion casts obtained injecting a range of experimental animals with a modified Batson's acrylic mixture.


Author(s):  
V. A. Maksimenko ◽  
A. A. Harchenko ◽  
A. Lüttjohann

Introduction: Now the great interest in studying the brain activity based on detection of oscillatory patterns on the recorded data of electrical neuronal activity (electroencephalograms) is associated with the possibility of developing brain-computer interfaces. Braincomputer interfaces are based on the real-time detection of characteristic patterns on electroencephalograms and their transformation  into commands for controlling external devices. One of the important areas of the brain-computer interfaces application is the control of the pathological activity of the brain. This is in demand for epilepsy patients, who do not respond to drug treatment.Purpose: A technique for detecting the characteristic patterns of neural activity preceding the occurrence of epileptic seizures.Results:Using multi-channel electroencephalograms, we consider the dynamics of thalamo-cortical brain network, preceded the occurrence of an epileptic seizure. We have developed technique which allows to predict the occurrence of an epileptic seizure. The technique has been implemented in a brain-computer interface, which has been tested in-vivo on the animal model of absence epilepsy.Practical relevance:The results of our study demonstrate the possibility of epileptic seizures prediction based on multichannel electroencephalograms. The obtained results can be used in the development of neurointerfaces for the prediction and prevention of seizures of various types of epilepsy in humans. 


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