scholarly journals Lactate is an energy substrate for rodent cortical neurons and enhances their firing activity

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Anastassios Karagiannis ◽  
Thierry Gallopin ◽  
Alexandre Lacroix ◽  
Fabrice Plaisier ◽  
Juliette Piquet ◽  
...  

Glucose is the mandatory fuel for the brain, yet the relative contribution of glucose and lactate for neuronal energy metabolism is unclear. We found that increased lactate, but not glucose concentration, enhances the spiking activity of neurons of the cerebral cortex. Enhanced spiking was dependent on ATP-sensitive potassium (KATP) channels formed with KCNJ11 and ABCC8 subunits, which we show are functionally expressed in most neocortical neuronal types. We also demonstrate the ability of cortical neurons to take-up and metabolize lactate. We further reveal that ATP is produced by cortical neurons largely via oxidative phosphorylation and only modestly by glycolysis. Our data demonstrate that in active neurons, lactate is preferred to glucose as an energy substrate, and that lactate metabolism shapes neuronal activity in the neocortex through KATP channels. Our results highlight the importance of metabolic crosstalk between neurons and astrocytes for brain function.

2021 ◽  
Author(s):  
Anastassios Karagiannis ◽  
Thierry Gallopin ◽  
Alexandre Lacroix ◽  
Fabrice Plaisier ◽  
Juliette Piquet ◽  
...  

Glucose is the mandatory fuel for the brain, yet the relative contribution of glucose and lactate for neuronal energy metabolism is unclear. We found that increased lactate, but not glucose concentration, enhances the spiking activity of neurons of the cerebral cortex. Enhanced spiking was dependent on ATP-sensitive potassium (KATP) channels formed with Kir6.2 and SUR1 subunits, which we show are functionally expressed in most neocortical neuronal types. We also demonstrate the ability of cortical neurons to take-up and metabolize lactate. We further reveal that ATP is produced by cortical neurons largely via oxidative phosphorylation and only modestly by glycolysis. Our data demonstrate that in active neurons, lactate is preferred to glucose as an energy substrate, and that lactate metabolism shapes neuronal activity in the neocortex through KATP channels. Our results highlight the importance of metabolic crosstalk between neurons and astrocytes for brain function.


1996 ◽  
Vol 84 (5) ◽  
pp. 1148-1155 ◽  
Author(s):  
Jerry M. Gonzales ◽  
Iris Mendez-Bobe

Background Cyclic adenosine monophosphate (cAMP) is an important regulator of neuronal excitability. The effects of barbiturates on cAMP production in intact neurons are not known. This study used cultures of cortical neurons, cultures of glia, and slices of cerebral cortex from the rat to study the effects of barbiturates on cAMP regulation in the brain. Methods Primary cultures of cortical neurons or glia were prepared from 17-day gestational Sprague-Dawley rat fetuses and were used after 12-16 days in culture. Cross-cut slices (300 microns) were prepared from cerebral cortex of adult rats. Cyclic AMP accumulation was determined by measuring the conversion of [3H]adenosine triphosphate (ATP) to [3H]cAMP in cells preloaded with [3H]adenine. Results Pentobarbital enhanced isoproterenol- and forskolin-stimulated, but not basal, cAMP accumulation in cultures of cerebral neurons. Cyclic AMP production was enhanced by pentobarbital in a dose-dependent fashion up to a concentration of 250 microM; This concentration of pentobarbital increased cAMP production by 40-50% relative to that in controls without pentobarbital. At 500 microM pentobarbital, the magnitude of the enhancement was less. Pentobarbital had no effect on isoproterenol-stimulated cAMP production in cultures containing only glia. Pentobarbital also enhanced isoproterenol-stimulated, but not basal, cAMP production in slices of cerebral cortex by approximately 30% at concentrations of 62.5-250 microM and by almost 100% at 500 microM. Conclusions Pentobarbital enhances stimulated cAMP accumulation in cultured preparations from brain and fresh cortical slices. Neurons are required for this effect. Because cAMP modulates neuronal excitability, this effect of pentobarbital may be an important mechanism by which this anesthetic influences brain function.


2017 ◽  
Vol 89 (1) ◽  
pp. 48-63 ◽  
Author(s):  
Sandra E. Dos Santos ◽  
Jairo Porfirio ◽  
Felipe B. da Cunha ◽  
Paul R. Manger ◽  
William Tavares ◽  
...  

In the effort to understand the evolution of mammalian brains, we have found that common relationships between brain structure mass and numbers of nonneuronal (glial and vascular) cells apply across eutherian mammals, but brain structure mass scales differently with numbers of neurons across structures and across primate and nonprimate clades. This suggests that the ancestral scaling rules for mammalian brains are those shared by extant nonprimate eutherians - but do these scaling relationships apply to marsupials, a sister group to eutherians that diverged early in mammalian evolution? Here we examine the cellular composition of the brains of 10 species of marsupials. We show that brain structure mass scales with numbers of nonneuronal cells, and numbers of cerebellar neurons scale with numbers of cerebral cortical neurons, comparable to what we have found in eutherians. These shared scaling relationships are therefore indicative of mechanisms that have been conserved since the first therians. In contrast, while marsupials share with nonprimate eutherians the scaling of cerebral cortex mass with number of neurons, their cerebella have more neurons than nonprimate eutherian cerebella of a similar mass, and their rest of brain has fewer neurons than eutherian structures of a similar mass. Moreover, Australasian marsupials exhibit ratios of neurons in the cerebral cortex and cerebellum over the rest of the brain, comparable to artiodactyls and primates. Our results suggest that Australasian marsupials have diverged from the ancestral Theria neuronal scaling rules, and support the suggestion that the scaling of average neuronal cell size with increasing numbers of neurons varies in evolution independently of the allocation of neurons across structures.


2019 ◽  
Vol 19 (3&4) ◽  
pp. 102
Author(s):  
Hossein Shamsi Gooshki ◽  
Seyyed Hassan Abedian Kalkhoran ◽  
Seyyed Mohammad Mahdi Ahmadi ◽  
Abolfazl Khoshi ◽  
Hassan Goodarzi

<p>The death of the cerebral cortex is a particular type of brain death that occurs after the destruction of the cerebral cortex (the hemispheres of the brain). It is said that the individual has gone through a vegetative state. This cortex is responsible for controlling voluntary activities of the body. This condition is caused by a coma (anesthesia), and sometimes the individual remains in this state for several years. Although the person looks awake, his/her eyes are open and has some involuntary movements, there is no signs of mental and cognitive function. Moreover, the individual is physically in a state of dementia. Coma is a state in which a person cannot be awakened and does not respond to any stimulation including pain. Generally it lasts few days to a few weeks, after which some patients gradually recover, but some permanently lose all brain function (brain death), while others evolve to a vegetative state (VS). Patients in VS are unconscious and unaware of their surroundings, but they continue to have a sleep-wake cycle and can have periods of consciousness. They are able to breathe spontaneously, retain their gag, cough, sucking, and swallowing reflexes. They often look fairly “normal” to families and friends who hope and pray for their full recovery. Laws and regulations in Islamic countries originate from popular jurisprudence. Therefore, by arguing that the well-known principles of Islam are necessarily legitimate, the phenomenon of vegetative state has been recognized. Jurisprudents have conflicting opinions on brain deaths and these perspectives cannot be considered as a widespread legal basis at the level of macro policy for administrative, medical and judicial affairs. In criminal law, maniac has no criminal responsibility because the punishment is not in line with the purpose of punishment. Consequently, restrictions will be imposed on the patients. Therefore, it can be concluded that a person with vegetative state is compatible with the insanity.</p>


1983 ◽  
Vol 103 (4) ◽  
pp. 509-520 ◽  
Author(s):  
J. van Doom ◽  
F. Roelfsema ◽  
D. van der Heide

Abstract. The effect of prolonged oral administration of PTU and MMI on the local conversion of T4 to T3 was studied in T4-maintained athyreotic rats. For this purpose the rats were equilibrated with [125I]T4 and [131I]T3 by means of continuous iv infusions. PTU treatment reduced the MCR of both T4 and T3, as well as the T3 levels in plasma, muscle, liver, kidney and cerebellum. In the cerebral cortex the total intracellular T3 concentration was not affected, while in the pituitary it even increased. The amount of T3 derived from local conversion of T4 to T3 (LcT3(T4)) was reduced in the liver. PTU treatment did not influence Lc T3(T4) in the cerebellum, but did cause an increase in the amount of T3 derived from this source in the cerebral cortex and the pituitary gland (both the homogenate and the nuclear fraction). The results indicate that in contrast to that in liver, local T3 production in the brain and pituitary must occur predominantly via a pathway which is not inhibited by PTU. In MMI-treated rats the total T3 concentration in the cerebral cortex and cerebellum was not altered, whereas both the MCR of T3 and the T3 levels in plasma and various other tissues were elevated. The relative contribution of Lc T3(T4) increased in liver and was reduced in the cerebral cortex, cerebellum and pituitary gland. In all experiments in liver the contribution of Lc T3(T4) to nuclear T3 was negligible, whereas this was not the case for the other hepatic subcellular fractions. As in liver, virtually all renal nuclear T3 was derived from plasma. The present findings suggest that the production of T3 in liver and kidney, and its subsequent release into the blood, may provide a mechanism for the regulation of plasma T3 levels but is not a direct source of their nuclear T3. In the pituitary gland and the brain local T4 to T3 conversion functions as a source of T3 for the control of local utilization. In this respect the maintainance of constant T3 levels in the brain might be important. These differences among tissues suggest that different mechanisms are involved in T4 5'-deiodination.


2020 ◽  
Author(s):  
Simona Sacchini ◽  
Josué Díaz ◽  
Antonio Espinosa de los Monteros ◽  
Yania Paz ◽  
Yara Bernaldo de Quirós ◽  
...  

Abstract Background: Alzheimer’s disease results from the interplay of multiple risk factors and their effects. Diving mammals may be routinely exposed to severe hypoxia when submerged. Among toothed whales, the beaked whales are particularly cryptic and routinely dive deeper than 1,000 m for about one hour in order to hunt deep-water squid and fish. We hypothesized that hypoxia could be a possible risk factor for neurodegenerative alterations in the central nervous system of beaked whales in particular, and toothed whales in general. Results: Samples of frontal cerebral cortex and cerebellum were collected from nine animals, representing six different species of the suborder Odontoceti. Immunohistochemical analysis employed a monoclonal anti-β-amyloid (Aβ) and a polyclonal anti-neurofibrillary tangle (NFT) antibodies. Six of nine (67%) animals showed positive immunolabeling for Aβ and/or NFT. The most striking findings were intranuclear Aβ immunopositivity in cerebral cortical neurons and NFT immunopositivity in cerebellar Purkinje neurons with granulovacuolar degeneration. Herein, we present immunohistopathological findings classic of Alzheimer’s and other neurodegenerative diseases in humans, in different brain locales of odontocete cetaceans. This study represents the first description of Aβ and NFT in the brain of beaked whales, adding also to the non-existent descriptions of GVD in the brain of non-experimental animals, being specifically the first report of granulovacuolar degeneration in the cerebellum. Our results further confirm the rarely reported intranuclear expression of Aβ. Conclusions: These findings could be linked to hypoxic phenomena, as they were more extensive in the brains of beaked whales, and not only in aged individuals. Therefore, a novel hypothesis linking hypoxia and neurodegeneration microscopic hallmarks in cetaceans is proposed. Despite their adaptations, diving mammals could be vulnerable to sustained and repetitive brain hypoxia. Future comparative pathological and neuroprotective investigations may prove of great value to Alzheimer’s disease and other neurodegenerative diseases in humans.


Author(s):  
S.S. Spicer ◽  
B.A. Schulte

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.


Author(s):  
Preecha Yupapin ◽  
Amiri I. S. ◽  
Ali J. ◽  
Ponsuwancharoen N. ◽  
Youplao P.

The sequence of the human brain can be configured by the originated strongly coupling fields to a pair of the ionic substances(bio-cells) within the microtubules. From which the dipole oscillation begins and transports by the strong trapped force, which is known as a tweezer. The tweezers are the trapped polaritons, which are the electrical charges with information. They will be collected on the brain surface and transport via the liquid core guide wave, which is the mixture of blood content and water. The oscillation frequency is called the Rabi frequency, is formed by the two-level atom system. Our aim will manipulate the Rabi oscillation by an on-chip device, where the quantum outputs may help to form the realistic human brain function for humanoid robotic applications.


Author(s):  
О.И. Кит ◽  
И.М. Котиева ◽  
Е.М. Франциянц ◽  
И.В. Каплиева ◽  
Л.К. Трепитаки ◽  
...  

Известно, что биогенные амины (БА) участвуют в злокачественном росте, их уровень изменяется в ЦНС при болевом воздействии, однако исследований о сочетанном влиянии хронической боли (ХБ) и онкопатологии на динамику БА в головном мозге не проводилось. Цель: изучить особенности баланса БА в коре головного мозга в динамике роста меланомы, воспроизведенной на фоне ХБ. Материалы и методы. Работа выполнена на 64 мышах-самках, весом 21-22 г. Животным основной группы меланому В16/F10 перевивали под кожу спины через 2 недели после перевязки седалищных нервов. Группой сравнения служили мыши с меланомой без боли. Уровни БА: адреналина, норадреналина, дофамина (ДА), серотонина (5-НТ), гистамина, а также 5-ОИУК определяли методом иммуноферментного анализа. Результаты. У мышей с ХБ уменьшается содержание большинства БА, однако уровень ДА не изменяется. Метаболизм 5-НТ происходит с участием МАО. Развитие меланомы сопровождается увеличением содержания ДА и 5-НТ, тогда как МАО - ингибируется. Направленность сдвигов БА при развитии меланомы на фоне ХБ оказалась практически такой же, как и без неё. В то же время ХБ ограничивает накопление 5-НТ в коре мозга при меланоме, что сопровождается более агрессивным её течением. Выводы. ХБ ограничивает включение стресс-лимитирующих механизмов в головном мозге при развитии меланомы у мышей, что приводит к более агрессивному течению злокачественного процесса. Biogenic amines (BA) are known to be involved in malignant growth, and their CNS levels change in pain; however, there are no studies of combined effects of chronic pain (CP) and cancer on BA dynamics in the brain. Aim: To study features of BA balance in the cerebral cortex during melanoma growth associated with CP. Material and methods. The study included 64 female mice weighing 21-22 g. In the main groups, B16/F10 melanoma was transplanted under the skin of the back two weeks following sciatic nerve ligation. Mice with melanoma without pain were used as the control. Concentrations of BA: adrenaline, noradrenaline, dopamine (DA), serotonin (5-HT), histamine and 5-HIAA were measured with ELISA. Results. Concentrations of BAs decreased in mice with CP although DA levels did not change. 5-HT metabolism involved MAO. The development of melanoma was accompanied by increases in DA and 5-HT whereas MAO was inhibited. The direction of BA changes during the development of melanoma was the same with and without CP. At the same time, CP with melanoma limited accumulation of 5-HT in the cerebral cortex, which resulted in even more aggressive course of cancer. Conclusion. CP restricted the activation of cerebral stress-limiting mechanisms during the development of melanoma in mice, which resulted in a more aggressive course of disease.


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