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1.
Article in English | MEDLINE | ID: mdl-39396145

ABSTRACT

BACKGROUND: This systematic review and meta-analysis qualitatively and quantitatively analyzes the current evidence on the implications of p53 upregulation in oral lichen planus (OLP) assessed by immunohistochemical techniques, in order to identify molecular mechanisms involved in the behavior of OLP as an oral potentially malignant disorder. MATERIAL AND METHODS: We searched MEDLINE/PubMed, Embase, Web of Science and Scopus for studies published before February-2024. We critically assessed the methodological quality of primary-level studies and performed meta-analyses. RESULTS: Twenty-four individual studies met the inclusion criteria, comprising 721 OLP samples, in which the expression of p53 was analyzed through immunohistochemistry. Most OLP displayed p53 protein upregulation (pooled proportion [PP]= 66.76%, 95%CI=54.84-77.76). Regarding the magnitude of association analysis, oral squamous cell carcinoma (OSCC) cases showed a significantly higher frequency according to p53 expression in comparison to OLP (OR=2.79, 95%CI=1.84-4.24; p<0.001); while, OLP exhibited a significantly higher frequency for p53 expression in comparison to healthy controls (OR=5.70, 95%CI=2.90-11.19; p<0.001). CONCLUSIONS: In conclusion, the present study demonstrates the frequent p53 protein upregulation in patients with OLP, which is probably indicating an antitumor response in an epithelium whose cells are under cellular stress and at risk of cancer.

2.
J Food Sci ; 89(9): 5302-5318, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39086065

ABSTRACT

The Mediterranean region is distinguished by its gastronomic diversity and a wide variety of indigenous nut crops. In line with changing global food consumers' preferences, a noteworthy aspect is the increasing demand to the use of local varieties in recipe formulation. The aim of the present study was to incorporate the Terra Fria chestnut (Portugal) and Negreta hazelnut from Reus (Spain) in traditional Mediterranean recipes. The sensory, technofunctional, nutritional, and shelf-life characterization were investigated in hazelnut omelette (gluten and gluten-free) and chestnut pudding (sugar and sugar-free) formulations. Results conducted by trained assessors using the free choice profiling (FCP) showed that hazelnut omelette samples were described as "creamy," "smooth," and "handmade." In addition, the texture obtained with the hazelnut omelette gluten-free version showed the softest textural profile analysis attributes, with lower values for hardness (2.43 ± 0.36 N), adhesiveness (-0.38 ± 0.00 g s) and gumminess (2.12 ± 0.14). Furthermore, the shelf-life studies revealed a more golden color (>14.43 of a* CIELAB coordinate) and a lower moisture content (25.36%-43.59%) in the hazelnut flour formulation, in addition to the enrichment in terms of protein (8.36 g/100 g), fiber, and healthy fats. In the case of chestnut pudding, it was observed that the study parameters did not differ significantly from its sweetened analogue with positive attributes in FCP ("toasted," "fluffy," and "sweet"), positioning it as a viable alternative to sugar in this application. Therefore, both hazelnut flour in hazelnut omelette and oligofructose in chestnut pudding proved to be promising ingredients in the formulation of gluten-free and sugar-free developed products, offering attractive organoleptic and textural characteristics.


Subject(s)
Corylus , Glutens , Nuts , Taste , Corylus/chemistry , Glutens/analysis , Nuts/chemistry , Humans , Diet, Gluten-Free , Food Handling/methods , Nutritive Value , Flour/analysis , Sugars/analysis , Spain
3.
Nat Commun ; 15(1): 6842, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39122700

ABSTRACT

Astrocytes control brain activity via both metabolic processes and gliotransmission, but the physiological links between these functions are scantly known. Here we show that endogenous activation of astrocyte type-1 cannabinoid (CB1) receptors determines a shift of glycolysis towards the lactate-dependent production of D-serine, thereby gating synaptic and cognitive functions in male mice. Mutant mice lacking the CB1 receptor gene in astrocytes (GFAP-CB1-KO) are impaired in novel object recognition (NOR) memory. This phenotype is rescued by the gliotransmitter D-serine, by its precursor L-serine, and also by lactate and 3,5-DHBA, an agonist of the lactate receptor HCAR1. Such lactate-dependent effect is abolished when the astrocyte-specific phosphorylated-pathway (PP), which diverts glycolysis towards L-serine synthesis, is blocked. Consistently, lactate and 3,5-DHBA promoted the co-agonist binding site occupancy of CA1 post-synaptic NMDA receptors in hippocampal slices in a PP-dependent manner. Thus, a tight cross-talk between astrocytic energy metabolism and gliotransmission determines synaptic and cognitive processes.


Subject(s)
Astrocytes , Cognition , Glycolysis , Lactic Acid , Mice, Knockout , Serine , Animals , Male , Astrocytes/metabolism , Cognition/physiology , Mice , Lactic Acid/metabolism , Serine/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Receptors, N-Methyl-D-Aspartate/genetics , Hippocampus/metabolism , Synapses/metabolism , Mice, Inbred C57BL , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/genetics
4.
bioRxiv ; 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39071354

ABSTRACT

We addressed the question of mitochondrial lactate metabolism using genetically-encoded sensors. The organelle was found to contain a dynamic lactate pool that leads to dose- and time-dependent protein lactylation. In neurons, mitochondrial lactate reported blood lactate levels with high fidelity. The exchange of lactate across the inner mitochondrial membrane was found to be mediated by a high affinity H+-coupled transport system involving the mitochondrial pyruvate carrier MPC. Assessment of electron transport chain activity and determination of lactate flux showed that mitochondria are tonic lactate producers, a phenomenon driven by energization and stimulated by hypoxia. We conclude that an overflow mechanism caps the redox level of mitochondria, while saving energy in the form of lactate.

5.
Article in English | MEDLINE | ID: mdl-38438188

ABSTRACT

Astrocytic metabolism has taken center stage. Interposed between the neuron and the vasculature, astrocytes exert control over the fluxes of energy and building blocks required for neuronal activity and plasticity. They are also key to local detoxification and waste recycling. Whereas neurons are metabolically rigid, astrocytes can switch between different metabolic profiles according to local demand and the nutritional state of the organism. Their metabolic state even seems to be instructive for peripheral nutrient mobilization and has been implicated in information processing and behavior. Here, we summarize recent progress in our understanding of astrocytic metabolism and its effects on metabolic homeostasis and cognition.


Subject(s)
Astrocytes , Brain , Astrocytes/metabolism , Brain/metabolism , Humans , Animals , Homeostasis , Neurons/metabolism , Energy Metabolism , Cognition/physiology
6.
Nat Neurosci ; 27(3): 433-448, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38267524

ABSTRACT

The integrity of myelinated axons relies on homeostatic support from oligodendrocytes (OLs). To determine how OLs detect axonal spiking and how rapid axon-OL metabolic coupling is regulated in the white matter, we studied activity-dependent calcium (Ca2+) and metabolite fluxes in the mouse optic nerve. We show that fast axonal spiking triggers Ca2+ signaling and glycolysis in OLs. OLs detect axonal activity through increases in extracellular potassium (K+) concentrations and activation of Kir4.1 channels, thereby regulating metabolite supply to axons. Both pharmacological inhibition and OL-specific inactivation of Kir4.1 reduce the activity-induced axonal lactate surge. Mice lacking oligodendroglial Kir4.1 exhibit lower resting lactate levels and altered glucose metabolism in axons. These early deficits in axonal energy metabolism are associated with late-onset axonopathy. Our findings reveal that OLs detect fast axonal spiking through K+ signaling, making acute metabolic coupling possible and adjusting the axon-OL metabolic unit to promote axonal health.


Subject(s)
Axons , White Matter , Mice , Animals , Axons/physiology , Oligodendroglia/metabolism , White Matter/metabolism , Homeostasis , Lactates/metabolism
7.
Nat Metab ; 5(11): 1852-1853, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37932429
8.
Oper Dent ; 48(6): 720-731, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37881067

ABSTRACT

OBJECTIVE: To evaluate the effects of commercial mouth rinses on color, roughness, sorption (SR), and solubility (SL) of resin composites. METHODS AND MATERIALS: Disc-shaped specimens (stage I: 6 mm × 2 mm; stage II: 10 mm × 1.5 mm) were made from the following resin composites (n=10): conventional nanofilled (Filtek Z350XT, 3M Oral Care), conventional nanohybrid (Luna, SDI), bulk-fill nanofilled (Filtek One Bulk-Fill, 3M Oral Care), and bulk-fill nanohybrid (Aura Bulk-Fill, SDI) exposed to distilled water (control), blue mouth rinse without alcohol (Colgate Total 12 Clean Mint, Colgate-Palmolive), or blue mouth rinse with alcohol and essential oil (Listerine Tartar Control, Johnson & Johnson). In stage I, tests were performed at the baseline, and after the immersion in solution time points to evaluate coordinates of the CIEL*a*b* system (ΔL*, Δa*, Δb*), general color change (ΔEab, ΔE00, and ΔSGU), and surface roughness (Ra). In stage II, SR and SL were evaluated (ISO 4049:2019) after immersion in the solutions for 7 days. The results were evaluated by generalized linear models (Ra, SR), Kruskal-Wallis, and Dunn tests (color, SL), with α = 0.05. RESULTS: There were no significative differences for Ra between the solutions. Both mouth rinses promoted significantly negative ΔL* (Luna), Δa* (Filtek One Bulk-fill), and Δb* (all materials except conventional nanofilled resin composite). Mouth rinse without alcohol promoted significantly negative Δa* on all resin composites tested. Both mouth rinses promoted higher ΔEab and ΔE00 for bulk-fill resin composites compared to control. Mouth rinse with alcohol caused higher ΔSGU for bulk-fill nanofilled resin composite. It also promoted greater SR in all the resin composites compared with mouth rinse without alcohol and higher SR in nanohybrid resin composites compared with control. Both mouth rinses promoted higher SL values in Luna and differed significantly from control. CONCLUSIONS: The physical properties were manufacturer dependent and mediated by mouth rinses. The mouth rinses promoted color changes in the resin composites, pointing out that bulk-fill resin composites were more affected by these effects, especially when the mouth rinse contained essential oil and alcohol.


Subject(s)
Mouthwashes , Oils, Volatile , Mouthwashes/pharmacology , Composite Resins , Ethanol , Solubility , Materials Testing , Surface Properties
9.
Oper Dent ; 48(6): 677-688, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37881103

ABSTRACT

OBJECTIVE: To evaluate the flexural strength of two types of high-viscosity resin composites (conventional or bulk-fill) that were repaired with either high-viscosity composites (conventional or bulk-fill) or low-viscosity composites (conventional or bulk-fill) of the same manufacturer (3M Oral Care, St Paul, MN, USA). METHODS AND MATERIALS: Specimens (25 mm × 2 mm × 2 mm) of both conventional nanofilled resin (Filtek Z350XT), and bulk-fill nanofilled resin (Filtek One Bulk Fill) were prepared. After fracture of the specimens in the 3-point bending test (initial), half of the specimens were repaired immediately afterwards (24 hours), and the other half were repaired after 6 months of storage in distilled water. Repairs were performed with (n=15) high-viscosity resin composites (Filtek Z350XT, Filtek One Bulk Fill), or their low-viscosity versions (Filtek Supreme XT Flow, Filtek Bulk Fill Flowable Restorative). The repair was performed by roughening the surface and applying phosphoric acid, silane, and adhesive. The bending test (results reported in MPa) was performed in a universal testing machine, and the fracture pattern was determined. Data were evaluated by generalized linear models, chi-square test and the Fisher exact test (α=0.05). RESULTS: There was no significant difference between the former pair of high-viscosity resins in terms of initial flexural strength (p=0.42). The repairs performed with low-viscosity resin composites after 24 hours or 6 months obtained higher MPa values compared with those using high-viscosity composites (p=0.0006). There was a significant decrease in MPa values when the repair was performed after 24 hours and an increase after 6 months, regardless of the material (p<0.0001). After 6 months, fractures involving the old (conventional) resin were more frequent in the repair performed with bulk-fill resin composites compared with the conventional composites (p=0.02). CONCLUSIONS: Considering the tested products, the material to be repaired did not influence the flexural strength of the repair composite; however, the use of the low-viscosity resin composites resulted in greater flexural strength of the repaired material. The repair of the aged composite resulted in an increase in its flexural strength, regardless of the material repaired or used to perform the repair.


Subject(s)
Dental Materials , Flexural Strength , Viscosity , Materials Testing , Composite Resins/therapeutic use
10.
Environ Toxicol Pharmacol ; 102: 104241, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37562547

ABSTRACT

The use of in vivo models to assess nephrotoxicity has faced ethical limitations. A viable alternative is the ex vivo model that combines the 3 R principles with the preservation of tissue histology. Here, we established a gentamicin nephrotoxicity model using pigs` kidney explants and investigated the effect of phytic acid (IP6) against gentamicin- induced nephrotoxicity. A total of 360 kidney explants were divided into control, gentamicin (10 mM), IP6 (5 mM), and gentamicin+IP6 groups. The activity of gammaglutamyltransferase (GGT), creatinine levels, histological assessment, oxidative stress, and inflammatory cytokine expression were analyzed. Exposure to gentamicin induced an increase in GGT activity, creatinine levels, lesion score, lipoperoxidation and IL-8 expression. Explants exposed to IP6 remained like the control. The addition of IP6 to gentamicin prevented tissue damage, increasing the antioxidant status and gene expression of IL-10. This model proved to be an adequate experimental approach for identifying nephrotoxins and potential products to modulate the toxicity.


Subject(s)
Kidney Diseases , Renal Insufficiency , Animals , Swine , Phytic Acid/pharmacology , Phytic Acid/therapeutic use , Phytic Acid/metabolism , Creatinine , Kidney , Antioxidants/pharmacology , Antioxidants/therapeutic use , Antioxidants/metabolism , Gentamicins/toxicity , Oxidative Stress , Kidney Diseases/pathology
11.
Neurobiol Dis ; 184: 106211, 2023 08.
Article in English | MEDLINE | ID: mdl-37352985

ABSTRACT

Brain tissue metabolism is distributed across several cell types and subcellular compartments, which activate at different times and with different temporal patterns. The introduction of genetically-encoded fluorescent indicators that are imaged using time-lapse microscopy has opened the possibility of studying brain metabolism at cellular and sub-cellular levels. There are indicators for sugars, monocarboxylates, Krebs cycle intermediates, amino acids, cofactors, and energy nucleotides, which inform about relative levels, concentrations and fluxes. This review offers a brief survey of the metabolic indicators that have been validated in brain cells, with some illustrative examples from the literature. Whereas only a small fraction of the metabolome is currently accessible to fluorescent probes, there are grounds to be optimistic about coming developments and the application of these tools to the study of brain disease.


Subject(s)
Brain , Fluorescent Dyes , Fluorescent Dyes/metabolism , Brain/metabolism , Metabolome , Energy Metabolism
12.
Aging (Albany NY) ; 15(19): 9896-9912, 2023 04 18.
Article in English | MEDLINE | ID: mdl-37074814

ABSTRACT

Dysregulated central-energy metabolism is a hallmark of brain aging. Supplying enough energy for neurotransmission relies on the neuron-astrocyte metabolic network. To identify genes contributing to age-associated brain functional decline, we formulated an approach to analyze the metabolic network by integrating flux, network structure and transcriptomic databases of neurotransmission and aging. Our findings support that during brain aging: (1) The astrocyte undergoes a metabolic switch from aerobic glycolysis to oxidative phosphorylation, decreasing lactate supply to the neuron, while the neuron suffers intrinsic energetic deficit by downregulation of Krebs cycle genes, including mdh1 and mdh2 (Malate-Aspartate Shuttle); (2) Branched-chain amino acid degradation genes were downregulated, identifying dld as a central regulator; (3) Ketone body synthesis increases in the neuron, while the astrocyte increases their utilization, in line with neuronal energy deficit in favor of astrocytes. We identified candidates for preclinical studies targeting energy metabolism to prevent age-associated cognitive decline.


Subject(s)
Astrocytes , Energy Metabolism , Astrocytes/metabolism , Energy Metabolism/genetics , Synaptic Transmission , Gene Expression Profiling , Glucose/metabolism
13.
Mol Neurodegener ; 18(1): 15, 2023 03 07.
Article in English | MEDLINE | ID: mdl-36882871

ABSTRACT

BACKGROUND: Major retinal degenerative diseases, including age-related macular degeneration, diabetic retinopathy and retinal detachment, are associated with a local decrease in oxygen availability causing the formation of hypoxic areas affecting the photoreceptor (PR) cells. Here, we addressed the underlying pathological mechanisms of PR degeneration by focusing on energy metabolism during chronic activation of hypoxia-inducible factors (HIFs) in rod PR. METHODS: We used two-photon laser scanning microscopy (TPLSM) of genetically encoded biosensors delivered by adeno-associated viruses (AAV) to determine lactate and glucose dynamics in PR and inner retinal cells. Retinal layer-specific proteomics, in situ enzymatic assays and immunofluorescence studies were used to analyse mitochondrial metabolism in rod PRs during chronic HIF activation. RESULTS: PRs exhibited remarkably higher glycolytic flux through the hexokinases than neurons of the inner retina. Chronic HIF activation in rods did not cause overt change in glucose dynamics but an increase in lactate production nonetheless. Furthermore, dysregulation of the oxidative phosphorylation pathway (OXPHOS) and tricarboxylic acid (TCA) cycle in rods with an activated hypoxic response decelerated cellular anabolism causing shortening of rod photoreceptor outer segments (OS) before onset of cell degeneration. Interestingly, rods with deficient OXPHOS but an intact TCA cycle did not exhibit these early signs of anabolic dysregulation and showed a slower course of degeneration. CONCLUSION: Together, these data indicate an exceeding high glycolytic flux in rods and highlight the importance of mitochondrial metabolism and especially of the TCA cycle for PR survival in conditions of increased HIF activity.


Subject(s)
Oxidative Phosphorylation , Retinal Degeneration , Humans , Glucose , Hypoxia , Lactic Acid , Retinal Rod Photoreceptor Cells
14.
Cell Mol Neurobiol ; 43(4): 1595-1618, 2023 May.
Article in English | MEDLINE | ID: mdl-35953741

ABSTRACT

Fiber intake is associated with a lower risk for Alzheimer´s disease (AD) in older adults. Intake of plant-based diets rich in soluble fiber promotes the production of short-chain fatty acids (SCFAs: butyrate, acetate, propionate) by gut bacteria. Butyrate administration has antiinflammatory actions, but propionate promotes neuroinflammation. In AD patients, gut microbiota dysbiosis is a common feature even in the prodromal stages of the disease. It is unclear whether the neuroprotective effects of fiber intake rely on gut microbiota modifications and specific actions of SCFAs in brain cells. Here, we show that restoration of the gut microbiota dysbiosis through the intake of soluble fiber resulted in lower propionate and higher butyrate production, reduced astrocyte activation and improved cognitive function in 6-month-old male APP/PS1 mice. The neuroprotective effects were lost in antibiotic-treated mice. Moreover, propionate promoted higher glycolysis and mitochondrial respiration in astrocytes, while butyrate induced a more quiescent metabolism. Therefore, fiber intake neuroprotective action depends on the modulation of butyrate/propionate production by gut bacteria. Our data further support and provide a mechanism to explain the beneficial effects of dietary interventions rich in soluble fiber to prevent dementia and AD. Fiber intake restored the concentration of propionate and butyrate by modulating the composition of gut microbiota in male transgenic (Tg) mice with Alzheimer´s disease. Gut dysbiosis was associated with intestinal damage and high propionate levels in control diet fed-Tg mice. Fiber-rich diet restored intestinal integrity and promoted the abundance of butyrate-producing bacteria. Butyrate concentration was associated with better cognitive performance in fiber-fed Tg mice. A fiber-rich diet may prevent the development of a dysbiotic microbiome and the related cognitive dysfunction in people at risk of developing Alzheimer´s disease.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Gastrointestinal Microbiome , Neuroprotective Agents , Mice , Animals , Propionates/pharmacology , Alzheimer Disease/metabolism , Gastrointestinal Microbiome/physiology , Dysbiosis , Neuroprotective Agents/pharmacology , Butyrates/pharmacology , Butyrates/metabolism , Dietary Fiber/pharmacology , Mice, Transgenic , Cognitive Dysfunction/prevention & control
15.
Annu Rev Physiol ; 85: 115-135, 2023 02 10.
Article in English | MEDLINE | ID: mdl-36270291

ABSTRACT

Information processing imposes urgent metabolic demands on neurons, which have negligible energy stores and restricted access to fuel. Here, we discuss metabolic recruitment, the tissue-level phenomenon whereby active neurons harvest resources from their surroundings. The primary event is the neuronal release of K+ that mirrors workload. Astrocytes sense K+ in exquisite fashion thanks to their unique coexpression of NBCe1 and α2ß2 Na+/K+ ATPase, and within seconds switch to Crabtree metabolism, involving GLUT1, aerobic glycolysis, transient suppression of mitochondrial respiration, and lactate export. The lactate surge serves as a secondary recruiter by inhibiting glucose consumption in distant cells. Additional recruiters are glutamate, nitric oxide, and ammonium, which signal over different spatiotemporal domains. The net outcome of these events is that more glucose, lactate, and oxygen are made available. Metabolic recruitment works alongside neurovascular coupling and various averaging strategies to support the inordinate dynamic range of individual neurons.


Subject(s)
Energy Metabolism , Glycolysis , Humans , Energy Metabolism/physiology , Glycolysis/physiology , Glucose/metabolism , Lactic Acid/metabolism , Brain/metabolism
16.
Orphanet J Rare Dis ; 17(1): 398, 2022 10 29.
Article in English | MEDLINE | ID: mdl-36309700

ABSTRACT

BACKGROUND: Congenital disorders of glycosylation (CDG) are a growing group of rare genetic disorders. The most common CDG is phosphomannomutase 2 (PMM2)-CDG which often has a severe clinical presentation and life-limiting consequences. There are no approved therapies for this condition. Also, there are no validated disease-specific quality of life (QoL) scales to assess the heterogeneous clinical burden of PMM2-CDG which presents a challenge for the assessment of the disease severity and the impact of a certain treatment on the course of the disease. AIM AND METHODS: This study aimed to identify the most impactful clinical signs and symptoms of PMM2-CDG, and specific patient and observer reported outcome measures (PROMs and ObsROMs, respectively) that can adequately measure such impact on patients' QoL. The most burdensome signs and symptoms were identified through input from the CDG community using a survey targeting PMM2-CDG families and experts, followed by family interviews to understand the real burden of these symptoms in daily life. The list of signs and symptoms was then verified and refined by patient representatives and medical experts in the field. Finally, a literature search for PROMs and ObsROMs used in other rare or common diseases with similar signs and symptoms to those of PMM2-CDG was performed. RESULTS: Twenty-four signs/symptoms were identified as the most impactful throughout PMM2-CDG patients' lifetime. We found 239 articles that included tools to measure those community-selected PMM2-CDG symptoms. Among them, we identified 80 QoL scales that address those signs and symptoms and, subsequently, their psychometric quality was analysed. These scales could be applied directly to the PMM2-CDG population or adapted to create the first PMM2-CDG-specific QoL questionnaire. CONCLUSION: Identifying the impactful clinical manifestations of PMM2-CDG, along with the collection of PROMs/ObsROMs assessing QoL using a creative and community-centric methodology are the first step towards the development of a new, tailored, and specific PMM2-CDG QoL questionnaire. These findings can be used to fill a gap in PMM2-CDG clinical development. Importantly, this methodology is transferable to other CDG and rare diseases with multiple signs and symptoms.


Subject(s)
Congenital Disorders of Glycosylation , Phosphotransferases (Phosphomutases) , Humans , Congenital Disorders of Glycosylation/drug therapy , Quality of Life , Glycosylation , Phosphotransferases (Phosphomutases)/genetics , Patient Reported Outcome Measures
17.
Proc Natl Acad Sci U S A ; 119(33): e2204619119, 2022 08 16.
Article in English | MEDLINE | ID: mdl-35939682

ABSTRACT

Brain activity is constrained by local availability of chemical energy, which is generated through compartmentalized metabolic processes. By analyzing data of whole human brain gene expression, we characterize the spatial distribution of seven glucose and monocarboxylate membrane transporters that mediate astrocyte-neuron lactate shuttle transfer of energy. We found that the gene coding for neuronal MCT2 is the only gene enriched in cerebral cortex where its abundance is inversely correlated with cortical thickness. Coexpression network analysis revealed that MCT2 was the only gene participating in an organized gene cluster enriched in K[Formula: see text] dynamics. Indeed, the expression of K[Formula: see text] subunits, which mediate lactate increases with spiking activity, is spatially coupled to MCT2 distribution. Notably, MCT2 expression correlated with fluorodeoxyglucose positron emission tomography task-dependent glucose utilization. Finally, the MCT2 messenger RNA gradient closely overlaps with functional MRI brain regions associated with attention, arousal, and stress. Our results highlight neuronal MCT2 lactate transporter as a key component of the cross-talk between astrocytes and neurons and a link between metabolism, cortical structure, and state-dependent brain function.


Subject(s)
Arousal , Attention , Cerebral Cortex , Lactic Acid , Monocarboxylic Acid Transporters , Neurons , Psychological Distress , Biological Transport , Cerebral Cortex/metabolism , Cerebral Cortex/ultrastructure , Glucose/metabolism , Humans , Lactic Acid/metabolism , Monocarboxylic Acid Transporters/genetics , Monocarboxylic Acid Transporters/metabolism , Neurons/metabolism , Positron-Emission Tomography
18.
Nat Commun ; 13(1): 2125, 2022 04 19.
Article in English | MEDLINE | ID: mdl-35440557

ABSTRACT

Neurovascular coupling is a fundamental brain mechanism that regulates local cerebral blood flow (CBF) in response to changes in neuronal activity. Functional imaging techniques are commonly used to record these changes in CBF as a proxy of neuronal activity to study the human brain. However, the mechanisms of neurovascular coupling remain incompletely understood. Here we show in experimental animal models (laboratory rats and mice) that the neuronal activity-dependent increases in local CBF in the somatosensory cortex are prevented by saturation of the CO2-sensitive vasodilatory brain mechanism with surplus of exogenous CO2 or disruption of brain CO2/HCO3- transport by genetic knockdown of electrogenic sodium-bicarbonate cotransporter 1 (NBCe1) expression in astrocytes. A systematic review of the literature data shows that CO2 and increased neuronal activity recruit the same vasodilatory signaling pathways. These results and analysis suggest that CO2 mediates signaling between neurons and the cerebral vasculature to regulate brain blood flow in accord with changes in the neuronal activity.


Subject(s)
Neurovascular Coupling , Animals , Carbon Dioxide/metabolism , Cerebral Cortex/metabolism , Cerebrovascular Circulation , Mice , Mice, Inbred C57BL , Rats , Sodium-Bicarbonate Symporters/genetics
19.
Appl Radiat Isot ; 184: 110122, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35272231

ABSTRACT

This work consists of an experimental determination of k0 and Q0 for 121Sb, 123Sb and 130Ba targets. Covariance analysis has been introduced to supply not only the overall uncertainties in these parameters but also their correlations. The irradiations were performed near the core of the IEA-R1 4.5 MW swimming-pool nuclear research reactor of the Nuclear and Energy Research Institute (IPEN-CNEN/SP), in São Paulo, Brazil. The epithermal neutron flux shape parameter, alpha, at the irradiation position is very close to zero, which favors to obtain Q0 values more accurately. Two irradiations were carried out in sequence, using two sets of samples: the first with bare samples and the second inside a Cd cover. The activity measurements were carried out in a previously calibrated HPGe gamma-ray spectrometer. The measurements were corrected for: saturation, decay time, cascade summing, geometry, self-attenuation, measuring time and mass. Standard sources of 152Eu, 133Ba, 60Co and 137Cs traceable to a 4πß-γ primary system were used to obtain the HPGe gamma-ray peak efficiency as a function of the energy. The experimental efficiency curve was performed by a fourth-degree polynomial fit, in the energy range of the standard sources, 121-1408 keV, it contains all correlations between points. For energies above 1408 keV, the efficiencies were obtained by the Monte Carlo Method. The covariance matrix methodology was applied to all uncertainties involved. The final values for k0 and Q0 were compared with the literature.


Subject(s)
Monte Carlo Method , Brazil
20.
Food Chem ; 383: 132450, 2022 Jul 30.
Article in English | MEDLINE | ID: mdl-35182861

ABSTRACT

Dehydration of the edible seaweed Chondrus crispus was performed by freeze-drying, conventional oven-drying and emerging microwave hydrodiffusion and gravity (MHG). In this work, the drying kinetics and modelling, estimating specific energy consumption and environmental impact of distinct processes were tested. Color and microstructural features of the dried macroalgae were also evaluated, as well as their nutritive characterization, chemical profile and bioactive potential (antioxidant and antimicrobial activities). Moreover, collected liquid phases from both the defrosted and MHG treated samples were also characterized. All methodologies provided solid phases with an adequate final moisture content. MHG significantly reduced the needed time, specific energy consumption and environmental impact, providing C. crispus with intermediate color and histological structure characteristics. Overall, this trend was also defined to tested chemical parameters and bioactivities. MHG provided aqueous extracts with potential bioactive compounds from this red alga, increasing the efficiency of this drying method.


Subject(s)
Chondrus , Seaweed , Antioxidants/chemistry , Chondrus/chemistry , Desiccation , Freeze Drying , Seaweed/chemistry , Vegetables
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