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

Sodium signaling and astrocyte energy metabolism DOI
Jean‐Yves Chatton, Pierre J. Magistretti, L. Felipe Barros

et al.

Glia, Journal Year: 2016, Volume and Issue: 64(10), P. 1667 - 1676

Published: March 29, 2016

The Na(+) gradient across the plasma membrane is constantly exploited by astrocytes as a secondary energy source to regulate intracellular and extracellular milieu, discard waste products. One of most prominent roles in brain -dependent clearance glutamate released neurons during synaptic transmission. load collectively generated these processes converges at Na,K-ATPase pump, responsible for extrusion from cell, which achieved expense cellular ATP. These represent pivotal mechanisms enabling increase local availability metabolic substrates response neuronal activity. This review presents basic principles linking handling following activity-related transmembrane fluxes pathways involved. We propose role an currency mediator signals context neuron-glia interactions. further discuss possible impact astrocytic syncytium distribution coordination response, compartmentation microdomains subcellular organelles. Finally, we illustrate future avenues investigation into signaling aimed bridging gap between machinery. GLIA 2016;64:1667-1676.

Language: Английский

Citations

65
Permissive role of cytosolic pH acidification in neurodegeneration: A closer look at its causes and consequences DOI
Alireza Majdi, Javad Mahmoudi, Saeed Sadigh‐Eteghad

et al.

Journal of Neuroscience Research, Journal Year: 2016, Volume and Issue: 94(10), P. 879 - 887

Published: June 10, 2016

The maintenance of cytosolic pH in its physiological range is required for normal neuronal activity, and even minor alterations can have serious consequences. This Review summarizes the current understanding conditions that are associated with disruption lead to abnormal acidification. Oxidative stress results acidification, this plays a crucial role emergence apoptosis protein misfolding excitotoxicity, ultimately leading irreversible damage. Through identification mechanisms by which intraneuronal acidification promotes neurodegeneration, we may identify new approaches preventing treating neurodegenerative disorders. © 2016 Wiley Periodicals, Inc.

Language: Английский

Citations

63
SypHer3s: a genetically encoded fluorescent ratiometric probe with enhanced brightness and an improved dynamic range DOI
Yulia G. Ermakova, Valeriy V. Pak, Yulia A. Bogdanova

et al.

Chemical Communications, Journal Year: 2018, Volume and Issue: 54(23), P. 2898 - 2901

Published: Jan. 1, 2018

We designed a genetically encoded ratiometric fluorescent probe, SypHer3s, with enhanced brightness and optimized pKa, which responds to pH changes in different cellular compartments.

Language: Английский

Citations

63
Protons as Messengers of Intercellular Communication in the Nervous System DOI Creative Commons

Enrique Soto,

Audrey Ortega-Ramírez, Rosario Vega

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2018, Volume and Issue: 12

Published: Oct. 10, 2018

Several studies demonstrated that the low pH of synaptic vesicles implies neurotransmitter release is always accompanied by co-release H+ into cleft, leading to transient extracellular shifts. Also, evidence has accumulated indicating various processes, including activation membrane transporters, increased production CO2 and metabolites, such as lactate, may produce significant shifts in nano- micro-domains central nervous system (CNS), constituting a reliable signal for intercellular communication. The mechanisms modulating proton concentration domains complex source protons network ion exchangers buffer capacity media finally establish or microdomains. Given strictly regulated variable multicellular organisms, localized changes constitute signals cellular processes occur cell group cells. ASICs function specific (not unique) sensors this signaling mechanism, detecting subtle variations range varying from 5 8. role extrasynaptic communication constitutes an old evolutionary have evolved metabolic state detection mechanism highly dependent mechanism. In study showing regulation its excitability systems reviewed, data regarding neurotransmission. Finally, we here propose relevant whose regulatory lead differential responses

Language: Английский

Citations

62
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

Citations

62