A5074625642- Neuroscience and Neuropharmacology Research
- Ion Transport and Channel Regulation
- Ion channel regulation and function
- Neuroscience of respiration and sleep
- Amino Acid Enzymes and Metabolism
- Mitochondrial Function and Pathology
- Adenosine and Purinergic Signaling
- Nitric Oxide and Endothelin Effects
- Neuroendocrine regulation and behavior
- Traumatic Brain Injury and Neurovascular Disturbances
- Heart Rate Variability and Autonomic Control
- Neuroinflammation and Neurodegeneration Mechanisms
- Sleep and Wakefulness Research
- Neuropeptides and Animal Physiology
- Neurogenesis and neuroplasticity mechanisms
- Diabetes Treatment and Management
- Regulation of Appetite and Obesity
- Pancreatic function and diabetes
- Connexins and lens biology
- Advanced MRI Techniques and Applications
- Bipolar Disorder and Treatment
- Sulfur Compounds in Biology
- Cardiac Ischemia and Reperfusion
- Apelin-related biomedical research
- Diet and metabolism studies
University College London
2017-2024
Lancaster University
2024
University of Kaiserslautern
2014-2019
Abstract Brain computation performed by billions of nerve cells relies on a sufficient and uninterrupted nutrient oxygen supply 1,2 . Astrocytes, the ubiquitous glial neighbours neurons, govern brain glucose uptake metabolism 3,4 , but exact mechanisms metabolic coupling between neurons astrocytes that ensure on-demand support neuronal energy needs are not fully understood 5,6 Here we show, using experimental in vitro vivo animal models, activity-dependent activation is mediated...
Abstract Astrocytes are implicated in modulation of neuronal excitability and synaptic function, but it remains unknown if these glial cells can directly control activities motor circuits to influence complex behaviors vivo. This study focused on the vital respiratory rhythm-generating preBötzinger (preBötC) determined how compromised function local astrocytes affects breathing conscious experimental animals (rats). Vesicular release mechanisms were disrupted by virally driven expression...
Brain cells continuously produce and release protons into the extracellular space, with rate of acid production corresponding to levels neuronal activity metabolism. Efficient buffering removal excess H+ is essential for brain function, not least because all electrogenic biochemical machinery synaptic transmission highly sensitive changes in pH. Here, we describe an astroglial mechanism that contributes protection milieu from acidification. In vivo vitro experiments conducted rodent models...
Ventral regions of the medulla oblongata brainstem are populated by astrocytes sensitive to physiological changes in P CO2 /[H + ]. These respond decreases pH with elevations intracellular Ca 2+ and facilitated exocytosis ATP-containing vesicles. Released ATP propagates excitation among neighboring activates neurons respiratory network triggering adaptive increases breathing. The mechanisms linking extracellular and/or ] responses chemosensitive remain unknown. Fluorescent imaging [Na i [Ca...
Mechanosensitivity is a well-known feature of astrocytes, however, its underlying mechanisms and functional significance remain unclear. There evidence that astrocytes are acutely sensitive to decreases in cerebral perfusion pressure may function as intracranial baroreceptors, tuned monitor brain blood flow. This study investigated the mechanosensory signaling brainstem these cells reside alongside cardiovascular control circuits mediate increases heart rate induced by falls perfusion. It...
Abstract Stroke remains one of the most common causes death and disability worldwide. Several preclinical studies demonstrated that brain can be effectively protected against ischaemic stroke by two seemingly distinct treatments: remote conditioning (RIC), involving cycles ischaemia/reperfusion applied to a peripheral organ or tissue, systemic administration glucagon-like-peptide-1 (GLP-1) receptor (GLP-1R) agonists. The mechanisms underlying RIC- GLP-1-induced neuroprotection are not...
The electrogenic sodium bicarbonate cotransporter NBCe1 ( SLC4A4 ) is a robust regulator of intracellular H + and significant base carrier in many cell types. Using wild-type (WT) NBCe1-deficient (NBC-KO) mice, we have studied the role cortical astrocytes culture situ by monitoring using -sensitive dye BCECF [2′,7′-bis-(carboxyethyl)-5-(and-6)-carboxyfluorescein] wide-field confocal microscopy. Adding 0.1–3 m HCO 3 − to an O 2 -gassed, HEPES-buffered saline solution lowered concentration...
During hypoxia, increases in cerebral blood flow maintain brain oxygen delivery. Here, we describe a mechanism of sensing that mediates the dilation intraparenchymal vessels response to reductions supply. In vitro and vivo experiments conducted rodent models show during cortical astrocytes produce potent vasodilator nitric oxide (NO) via nitrite reduction mitochondria. Inhibition mitochondrial respiration mimics, but also occludes, effect hypoxia on NO production astrocytes. Astrocytes...
The regulation of H(+) i from cytosolic alkalosis has generally been attributed to the activity Cl(-) -coupled acid loaders/base extruders in most cell types, including brain cells. present study demonstrates that outwardly-directed sodium bicarbonate cotransport via electrogenic cotransporter 1 (NBCe1) mediates major fraction mouse cortical astrocytes. acid-loading transporters play only a minor role NBCe1-mediated was dominant, with support intracellular carbonic anhydrase II, even when...
Cytosolic H + buffering plays a major role for shaping intracellular shifts and hence the availability of biochemical reactions acid/base‐coupled transport processes. is one prime means to protect cell from large acid/base shifts. We have used indicator dye BCECF confocal microscopy monitor cytosolic concentration, [H ] i , in cultured cortical astrocytes wild‐type mice deficient sodium/bicarbonate cotransporter NBCe1 (NBCe1‐KO) or carbonic anhydrase isoform II (CAII‐KO). The steady‐state...
Maintenance of cardiorespiratory homeostasis depends on autonomic reflexes controlled by neuronal circuits the brainstem. The neurophysiology and neuroanatomy these reflex pathways are well understood, however, mechanisms functional significance circuit modulation glial cells remain largely unknown. In experiments conducted in male laboratory rats we show that astrocytes nucleus solitary tract (NTS), brain area receives integrates sensory information from heart blood vessels, respond to...
Glycolysis is the primary step for major energy production in cell. There strong evidence suggesting that glucose consumption and rate of glycolysis are highly modulated by cytosolic pH/[H+], but those can also be stimulated an increase intracellular [HCO3−]. Because proton bicarbonate shift concomitantly, it remained unclear whether enhanced glycolytic were mediated changes [H+] or We have asked metabolism either a fall rise [HCO3−], both, mammalian astrocytes. recorded mouse astrocytes...
The present study suggests that the electrogenic sodium-bicarbonate cotransporter, NBCe1, supported by carbonic anhydrase II, CAII, provides an efficient mechanism of bicarbonate sensing in cortical astrocytes. This is proposed to play a major role setting pHi responses extracellular acid/base challenges A decrease [HCO3- ] during isocapnic acidosis and isohydric hypocapnia, or increase intracellular hypercapnic acidosis, was effectively sensed which carried out cells under these conditions,...
OPINION article Front. Neurosci., 05 January 2015Sec. Neuroenergetics, Nutrition and Brain Health https://doi.org/10.3389/fnins.2014.00430
The effects of anaesthetic agents on brain energy metabolism may explain their shared neurophysiological actions but remain poorly understood. lactate shuttle hypothesis proposes that lactate, provided by astrocytes, is an important neuronal substrate. Here we tested the impair interfering with astrocytic glycolysis. Lactate biosensors were used to record changes in release adult rat brainstem and cortical slices response thiopental, propofol etomidate. Changes cytosolic nicotinamide adenine...
Sodium plays a major role in different astrocytic functions, including maintenance of ion homeostasis and uptake neurotransmitters metabolites, which are mediated by Na+ -coupled transporters. In the current study, an electrogenic sodium-bicarbonate cotransporter (NBCe1), sodium-potassium-chloride transporter 1 (NKCC1) sodium-potassium ATPase (Na+ -K+ -ATPase) for [Na+ ]i was investigated cultured astrocytes wild-type (WT) NBCe1-deficient (NBCe1-KO) mice using -sensitive dye, asante sodium...
The electrogenic sodium bicarbonate cotransporter NBCe1 ( SLC4A4 ) is expressed in many cell types and a major regulator of intracellular, extracellular pH. In astrocytes, membrane depolarization leads to intracellular alkalinization through the activation NBCe1. However, molecular mechanisms regulating functional expression astrocytes are largely unknown. Astrocytes also express voltage‐dependent K + channels that activated after sensitive blocker 4‐aminopyridine (4AP). Using acute...
Abstract The electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), is the major transporter expressed in astrocytes. It highly sensitive for and main regulator of intracellular, extracellular, synaptic pH, thereby modulating neuronal excitability. However, despite these essential functions, molecular mechanisms underlying NBCe1‐mediated astrocytic response to extracellular pH changes are mostly unknown. Using primary mouse cortical astrocyte cultures, we investigated effect...
Abstract: Our brain, which accounts for about 2 % of our body weight, uses up to 20 total energy requirements. The supply with sufficient energetic substrates all brain cells, are very densely packed, in particular the human is a huge logistic challenge. most important substrate glucose, reaches via blood circulation. Glucose not only utilized by nerve cells directly, but large extent also taken glial then either store glucose after conversion glycogen as reserve, or transfer it lactate...