Measurement of lactate levels in postmortem brain, iPSCs, and animal models of schizophrenia DOI Creative Commons
Courtney R. Sullivan, Catharine A. Mielnik, Adam Funk

et al.

Scientific Reports, Journal Year: 2019, Volume and Issue: 9(1)

Published: March 25, 2019

Abstract Converging evidence suggests bioenergetic defects contribute to the pathophysiology of schizophrenia and may underlie cognitive dysfunction. The transport metabolism lactate energetically couples astrocytes neurons supports brain bioenergetics. We examined concentration in postmortem (dorsolateral prefrontal cortex) subjects with schizophrenia, two animal models GluN1 knockdown mouse model mutant disrupted 1 (DISC1) model, as well inducible pluripotent stem cells (iPSCs) from a subject DISC1 mutation. found increased dorsolateral cortex (p = 0.043, n 16/group) frontal cortical differentiated mutation 0.032). also decrease mice induced expression human specifically 0.049). These results build upon body supporting dysfunction changes are key feature this often devastating severe mental illness.

Language: Английский

Neuronal-Glial Interactions Maintain Chronic Neuropathic Pain after Spinal Cord Injury DOI Creative Commons
Young Seob Gwak, Claire E. Hulsebosch, Joong Woo Leem

et al.

Neural Plasticity, Journal Year: 2017, Volume and Issue: 2017, P. 1 - 14

Published: Jan. 1, 2017

The hyperactive state of sensory neurons in the spinal cord enhances pain transmission. Spinal glial cells have also been implicated enhanced excitability dorsal horn neurons, resulting amplification and distortions. Traumatic injuries neural system such as injury (SCI) induce neuronal hyperactivity activation, causing maladaptive synaptic plasticity cord. Recent studies demonstrate that SCI causes persistent activation with concomitant hyperactivity, thus providing substrate for central neuropathic pain. Hyperactive activated increase intracellular extracellular glutamate, neuropeptides, adenosine triphosphates, proinflammatory cytokines, reactive oxygen species concentrations, all which enhance In addition, overexpress receptors ion channels maintain this Therefore, post-SCI neuronal-glial interactions create circuits activate signaling events permanently contribute to review, we describe how contributes maintenance chronic via following SCI.

Language: Английский

Citations

104

Acid-base physiology and CO2 homeostasis: Regulation and compensation in response to elevated environmental CO2 DOI
Colin J. Brauner, Ryan B. Shartau, Christian Damsgaard

et al.

Fish physiology, Journal Year: 2019, Volume and Issue: unknown, P. 69 - 132

Published: Jan. 1, 2019

Language: Английский

Citations

78

Sterile neutrinos and neutrinoless double beta decay in effective field theory DOI Creative Commons
Wouter Dekens, Jordy de Vries, Kaori Fuyuto

et al.

Journal of High Energy Physics, Journal Year: 2020, Volume and Issue: 2020(6)

Published: June 1, 2020

We investigate neutrinoless double beta decay (0νββ) in the presence of sterile neutrinos with Majorana mass terms. These gauge-singlet fields are allowed to interact Standard-Model (SM) via renormalizable Yukawa couplings as well higher-dimensional gauge-invariant operators up dimension seven Standard Model Effective Field Theory extended neutrinos. At GeV scale, we use Chiral effective field theory involving connect at level quarks and gluons hadronic interactions pions nucleons. This allows us derive an expression for 0νββ rates various isotopes terms phase-space factors, low-energy constants, nuclear matrix elements, neutrino masses, Wilson coefficients operators. The required constants elements depend on which obtain interpolation formulae grounded QCD chiral perturbation that improve existing only valid a small regime masses. resulting framework can be used directly assess impact experiments scenarios light should prove useful global analyses sterile-neutrino searches. per- form several phenomenological studies without find non-standard have dramatic phenomenology, next-generation probe such scales $$ \mathcal{O} (100) TeV.

Language: Английский

Citations

74

Determinants, maintenance, and function of organellar pH DOI
Spencer A. Freeman, Sergio Grinstein, John Orlowski

et al.

Physiological Reviews, Journal Year: 2022, Volume and Issue: 103(1), P. 515 - 606

Published: Aug. 18, 2022

The protonation state of soluble and membrane-associated macromolecules dictates their charge, conformation, functional activity. In addition, protons (H + or equivalents) partake in numerous metabolic reactions serve as a source electrochemical energy to drive the transmembrane transport both organic inorganic substrates. Stringent regulation intracellular pH is therefore paramount homeostasis. Although cytosolic has been studied extensively, our understanding determinants H concentration ([H ]) organelles developed more slowly, limited by small size inaccessibility. Recently, however, targeting molecular probes organellar lumen together with advances genomic, proteomic, electrophysiological techniques have led identification characterization unique pumps, channels, transporters responsible for establishment maintenance intraorganellar pH. These developments implications cellular function health disease are subject this review.

Language: Английский

Citations

53

Effects of pH alterations on stress- and aging-induced protein phase separation DOI Creative Commons
Xuejiao Jin, Min Zhou, Shuxin Chen

et al.

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(7)

Published: June 24, 2022

Abstract Upon stress challenges, proteins/RNAs undergo liquid–liquid phase separation (LLPS) to fine-tune cell physiology and metabolism help cells adapt adverse environments. The formation of LLPS has been recently linked with intracellular pH, maintaining proper pH homeostasis is known be essential for the survival organisms. However, organisms are constantly exposed diverse stresses, which accompanied by alterations in pH. Aging processes human diseases also intimately alterations. In this review, we summarize stress-, aging-, cancer-associated changes together mechanisms regulate cytosolic homeostasis. How critical components response discussed, along functional roles fluctuation regulation LLPS. Further studies investigating interplay other stressors identifying protein responses different levels will provide an in-depth understanding underlying pH-driven adaptation. Moreover, deciphering aging disease-associated that influence condensate could lead a deeper biomolecular condensates aging-related diseases.

Language: Английский

Citations

50

Spectral fiber photometry derives hemoglobin concentration changes for accurate measurement of fluorescent sensor activity DOI Creative Commons
Weiting Zhang, Tzu-Hao Harry Chao, Yue Yang

et al.

Cell Reports Methods, Journal Year: 2022, Volume and Issue: 2(7), P. 100243 - 100243

Published: June 29, 2022

Fiber photometry is an emerging technique for recording fluorescent sensor activity in the brain. However, significant hemoglobin absorption artifacts fiber data may be misinterpreted as changes. Because exists widely brain, and its concentration varies temporally, such could impede accuracy of recordings. Here we present use spectral computational methods to quantify photon effects by using activity-independent fluorescence signals, which can used derive oxy- deoxy-hemoglobin Although these changes are often temporally delayed compared with fast-responding spikes, found that erroneous interpretation occur when examining pharmacology-induced sustained sometimes flip GCaMP signal polarity. We provide hemoglobin-based correction restore signals compare our results other commonly approaches. also demonstrated utility delineating regional differences hemodynamic response functions.

Language: Английский

Citations

40

pH regulating mechanisms of astrocytes: A critical component in physiology and disease of the brain DOI Creative Commons
Shefeeq M. Theparambil, Gulnaz Begum, Christine R. Rose

et al.

Cell Calcium, Journal Year: 2024, Volume and Issue: 120, P. 102882 - 102882

Published: April 8, 2024

Strict homeostatic control of pH in both intra- and extracellular compartments the brain is fundamentally important, primarily due to profound impact free protons ([H

Language: Английский

Citations

9

Physiological Roles of Acid-Base Sensors DOI
Lonny R. Levin, Jochen Buck

Annual Review of Physiology, Journal Year: 2014, Volume and Issue: 77(1), P. 347 - 362

Published: Oct. 23, 2014

Acid-base homeostasis is essential for life. The macromolecules upon which living organisms depend are sensitive to pH changes, and physiological systems use the equilibrium between carbon dioxide, bicarbonate, protons buffer their pH. Biological processes environmental insults constantly challenging an organism's pH; therefore, maintain a consistent proper pH, need sensors that measure elicit appropriate responses. Mammals multiple measuring both intracellular extracellular although some mammalian directly protons, it has recently become apparent many pH-sensing via bicarbonate-sensing soluble adenylyl cyclase.

Language: Английский

Citations

94

Cellular acidification as a new approach to cancer treatment and to the understanding and therapeutics of neurodegenerative diseases DOI
Salvador Harguindey,

Daniel Stanciu,

Jesús Devesa

et al.

Seminars in Cancer Biology, Journal Year: 2017, Volume and Issue: 43, P. 157 - 179

Published: Feb. 11, 2017

Language: Английский

Citations

70

Emerging roles of Na+/H+ exchangers in epilepsy and developmental brain disorders DOI

Hanshu Zhao,

Karen E. Carney,

Lindsay Falgoust

et al.

Progress in Neurobiology, Journal Year: 2016, Volume and Issue: 138-140, P. 19 - 35

Published: March 1, 2016

Language: Английский

Citations

67