D-serine released by astrocytes in brainstem regulates breathing response to CO2 levels

Beltrán-Castillo, Sebastián; Olivares, María José; Contreras, Rodrigo A.; Zúñiga, Gustavo E.; Llona, Isabel; Bernhardi, Rommy von; Eugenı́n, Jaime

doi:10.1038/s41467-017-00960-3

Cited by 61 publications

(69 citation statements)

References 69 publications

(89 reference statements)

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“…The actual real specificity of these compounds remains unknown and could display unwanted off-target effects as illustrated for OHAsp, PES and PM, which have been largely used to inhibit SR [42][43][44][45][46][47][48] Therefore, the specificity of a putative inhibitor has to be first validated in SR −/− or DAAO −/− mice, depending on the target of the compound. The actual real specificity of these compounds remains unknown and could display unwanted off-target effects as illustrated for OHAsp, PES and PM, which have been largely used to inhibit SR [42][43][44][45][46][47][48] Therefore, the specificity of a putative inhibitor has to be first validated in SR −/− or DAAO −/− mice, depending on the target of the compound.…”

Section: Pharmacological Inhibition Of D-serine Function and Metabolimentioning

confidence: 99%

“…An example is given by the use of fluoroacetate (FAC) to block metabolism of glial cells and then the pharmacological rescue by adding exogenous D-serine to restore normal function. 43 These effects have been ascribed to the blockade of astrocytic D-serine release by FAC (but only based on the observation that adding exogenous D-serine rescues these NMDAR-dependent functions; see 17,58 ). 58 When brain tissues are exposed to FAC, it is converted into fluorocitrate, an inhibitor of aconitase, and hence impairs the tricarboxylic acid (TCA) cycle in astrocytes.…”

Section: Poisoning and Pharmacological Rescue Experimentsmentioning

confidence: 99%

“…73 Using this enzymatic approach, D-serine was shown to be the primary NMDAR co-agonist required for LTP at many CNS synapses, 28,41,50,73,74 or to be required for the LTD at synapses between parallel fibers and Purkinje cells in the immature cerebellum. Important observations have been reported proposing that D-serine mediates the spread of gliogenic LTP in nociceptive pathways, 78 neuropathic pain depends upon D-serine co-activation of spinal NMDARs in rats, 61,62 D-serine released by astrocytes in the brainstem regulates breathing response to CO 2 levels, 43 and glial D-serine controls synaptic metaplasticity in the hypothalamus. SR −/− mice have a 90% decrease in brain D-serine and show reduced NMDAR currents, impaired synaptic plasticity, and learning deficits.…”

Section: Off-target Effects Of Some Genetic and Pharmacological Toomentioning

confidence: 99%

“…When OHAsp was bath applied, it increased locomotor-related activity recorded from the ventral roots of spinal cord preparations from neonatal mice, 45 an effect opposed to the application of DAAO (commercial source). 43 In all these studies, the inhibitory effects of the compounds were counteracted by application of D-serine and were opposed to the enzymatic degradation of D-serine by applied DAAO, just apparently warranting the use of the SR inhibitors. 47 Application of PES and PMS to neonatal mouse cerebellum slices impedes neuronal migration 48 and also decreases respiratory frequency when applied to brainstem slices.…”

Section: Off-target Effects Of Some Genetic and Pharmacological Toomentioning

confidence: 99%

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Investigating brain d‐serine: Advocacy for good practices

et al. 2019

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The last two decades have witnessed remarkable advance in our understanding the role of D-amino acids in the mammalian nervous system: from the unknown, to known molecules with unknown functions, to potential central players in health and disease. D-Amino acids have emerged as an important class of signaling molecules. In particular, the exploration of the roles of D-serine in brain physiopathology is a vibrant field that is growing at an accelerating pace. However, disentangling the functions of a chiral molecule in a complex chemical matrice as the brain requires specific measurement and detection methods but is also a challenging task as many molecular tools and models investigators are using can lead to confounded observations. Thus, study of D-amino acids demands accurate methodologies and specific controls, and these have often been lacking. Here we outline best practices for D-amino acid research, with a special emphasis on D-serine. We hope these concepts help move the field to greater rigor and reproducibility, allowing the field to advance. K E Y W O R D Sanalytical methods, D-Serine, glia, immunostainings, neurons, NMDA receptors, rescue experiments, serine racemase inhibitors

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Section: Pharmacological Inhibition Of D-serine Function and Metabolimentioning

confidence: 99%

Section: Poisoning and Pharmacological Rescue Experimentsmentioning

confidence: 99%

Section: Off-target Effects Of Some Genetic and Pharmacological Toomentioning

confidence: 99%

Section: Off-target Effects Of Some Genetic and Pharmacological Toomentioning

confidence: 99%

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Investigating brain d‐serine: Advocacy for good practices

et al. 2019

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“…) and d ‐serine (Beltrán‐Castillo et al . ). ATP release has been proposed to be facilitated by connexin hemichannels (Huckstepp et al .…”

Section: Introductionmentioning

confidence: 97%

Advances in cellular and integrative control of oxygen homeostasis within the central nervous system

Ramírez

Severs

Ramirez

et al. 2018

The Journal of Physiology

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Mammals must continuously regulate the levels of O and CO , which is particularly important for the brain. Failure to maintain adequate O /CO homeostasis has been associated with numerous disorders including sleep apnoea, Rett syndrome and sudden infant death syndrome. But, O /CO homeostasis poses major regulatory challenges, even in the healthy brain. Neuronal activities change in a differentiated, spatially and temporally complex manner, which is reflected in equally complex changes in O demand. This raises important questions: is oxygen sensing an emergent property, locally generated within all active neuronal networks, and/or the property of specialized O -sensitive CNS regions? Increasing evidence suggests that the regulation of the brain's redox state involves properties that are intrinsic to many networks, but that specialized regions in the brainstem orchestrate the integrated control of respiratory and cardiovascular functions. Although the levels of O in arterial blood and the CNS are very different, neuro-glial interactions and purinergic signalling are critical for both peripheral and CNS chemosensation. Indeed, the specificity of neuroglial interactions seems to determine the differential responses to O , CO and the changes in pH.

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Enantiospecific Detection of D‐Amino Acid through Synergistic Upconversion Energy Transfer

et al. 2021

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D‐amino acids (DAAs) are indispensable in regulating diverse metabolic pathways. Selective and sensitive detection of DAAs is crucial for understanding the complexity of metabolic processes and managing associated diseases. However, current DAA detection strategies mainly rely on bulky instrumentation or electrochemical probes, limiting their cellular and animal applications. Here we report an enzyme‐coupled nanoprobe that can detect enantiospecific DAAs through synergistic energy transfer. This nanoprobe offers near‐infrared upconversion capability, a wide dynamic detection range, and a detection limit of 2.2 μM, providing a versatile platform for in vivo noninvasive detection of DAAs with high enantioselectivity. These results potentially allow real‐time monitoring of biomolecular handedness in living animals, as well as developing antipsychotic treatment strategies.

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D-serine released by astrocytes in brainstem regulates breathing response to CO2 levels

Cited by 61 publications

References 69 publications

Investigating brain d‐serine: Advocacy for good practices

Investigating brain d‐serine: Advocacy for good practices

Advances in cellular and integrative control of oxygen homeostasis within the central nervous system

Enantiospecific Detection of D‐Amino Acid through Synergistic Upconversion Energy Transfer

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