Astroglial Versus Neuronal D-Serine: Check Your Controls!

Wolosker, Herman; Balu, Darrick T.; Coyle, Joseph T.

doi:10.1016/j.tins.2017.06.010

Cited by 46 publications

(32 citation statements)

References 13 publications

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“…[91][92][93] However, the primary site of synthesis and release of d-Ser remains controversial. 94 SR catalyzes both the racemization and the α,β-elimination of serine enantiomers 95 and therefore has ability to both synthesize and degrade d-Ser. Wolosker proposed an astrocyte-neuron communication model in the forebrain area involving the exchange of serine enantiomers, called "the serine shuttle," whereby astrocytes synthesize and export the l-Ser required for the synthesis of d-Ser by the predominantly neuronal SR. 96 Neuronal and glial d-Ser production depends on the l-Ser produced by the astrocytic enzyme 3-phosphoglycerate dehydrogenase.…”

Section: Physiological Role Of D-serine In Mammals: Neurotransmissionmentioning

confidence: 99%

Distinctive Roles of D-Amino Acids in the Homochiral World: Chirality of Amino Acids Modulates Mammalian Physiology and Pathology

Sasabe

Suzuki

2018

Keio J. Med.

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Living organisms enantioselectively employ L-amino acids as the molecular architecture of protein synthesized in the ribosome. Although L-amino acids are dominantly utilized in most biological processes, accumulating evidence points to the distinctive roles of D-amino acids in non-ribosomal physiology. Among the three domains of life, bacteria have the greatest capacity to produce a wide variety of D-amino acids. In contrast, archaea and eukaryotes are thought generally to synthesize only two kinds of D-amino acids: D-serine and D-aspartate. In mammals, D-serine is critical for neurotransmission as an endogenous coagonist of N-methyl D-aspartate receptors. Additionally, D-aspartate is associated with neurogenesis and endocrine systems. Furthermore, recognition of D-amino acids originating in bacteria is linked to systemic and mucosal innate immunity. Among the roles played by D-amino acids in human pathology, the dysfunction of neurotransmission mediated by D-serine is implicated in psychiatric and neurological disorders. Non-enzymatic conversion of L-aspartate or L-serine residues to their D-configurations is involved in age-associated protein degeneration. Moreover, the measurement of plasma or urinary D-/L-serine or D-/L-aspartate levels may have diagnostic or prognostic value in the treatment of kidney diseases. This review aims to summarize current understanding of D-amino-acid-associated biology with a major focus on mammalian physiology and pathology.

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Section: Physiological Role Of D-serine In Mammals: Neurotransmissionmentioning

confidence: 99%

Distinctive Roles of D-Amino Acids in the Homochiral World: Chirality of Amino Acids Modulates Mammalian Physiology and Pathology

Sasabe

Suzuki

2018

Keio J. Med.

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“…Serine racemase is expressed by many CNS cells, including pyramidal neurons in the cerebral cortex, gamma-aminobutyric acid (GABA) ergic medium-spiny neurons in the striatum, cerebellar GABAergic Purkinje cells [ 28 ], vestibular nuclei neurons [ 29 ], astrocytes from the caudal medulla oblongata [ 11 ], telencephalon, and the CA1 region of the hippocampus [ 22 ], and neurons and astrocytes from the retina [ 30 , 31 ]. However, which cells are the principal source of D-serine release in the CNS is still controversial [ 32 , 33 ]. The predominant source appears to depend on the CNS area, function, developmental stage, and inflammatory state [ 7 , 8 , 11 , 31 , 34 , 35 ].…”

Section: D-serine In the Cnsmentioning

confidence: 99%

“…How much of the changes in D-serine level during aging are determined by microglial cell actions has not been elucidated. However, we speculate that age-dependent changes on microglia regulation results in neuroinflammation and increased oxidative stress, which in turn activate production of D-serine by astrocytes and neurons [ 33 , 71 , 109 – 112 ]. Thus, aging on the one hand can promote overactivation of glutamatergic by increased D-serine level and on the other result in impaired activation.…”

Section: Role Of D-serine In Cns Development and Cns Levels In Agimentioning

confidence: 99%

Impact of Aging in Microglia-Mediated D-Serine Balance in the CNS

Beltrán-Castillo

Eugenı́n

Bernhardi

2018

Mediators of Inflammation

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A mild chronic inflammatory state, like that observed in aged individuals, affects microglial function, inducing a dysfunctional phenotype that potentiates neuroinflammation and cytotoxicity instead of neuroprotection in response to additional challenges. Given that inflammatory activation of microglia promotes increased release of D-serine, we postulate that age-dependent inflammatory brain environment leads to microglia-mediated changes on the D-serine-regulated glutamatergic transmission. Furthermore, D-serine dysregulation, in addition to affecting synaptogenesis and synaptic plasticity, appears also to potentiate NMDAR-dependent excitotoxicity, promoting neurodegeneration and cognitive impairment. D-serine dysregulation promoted by microglia could have a role in age-related cognitive impairment and in the induction and progression of neurodegenerative processes like Alzheimer's disease.

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“…Glycine generally arises from astroglial cells but could also have a neuronal origin (Harsing & Matyus, ). Concerning the origin of D‐serine it is not clear whether the co‐agonist originates exclusively from glial cells (Papouin, Henneberger, Rusakov, & Oliet, ) or from neurons (Wolosker, Balu, & Coyle, ).…”

Section: Introductionmentioning

confidence: 99%

Subsaturation of the N‐methyl‐D‐aspartate receptor glycine site allows the regulation of bursting activity in juvenile rat nigral dopamine neurons

Destreel

Seutin

Engel

2019

Eur J of Neuroscience

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The activation of N‐methyl‐D‐aspartate receptors (NMDARs) in substantia nigra pars compacta (SNc) dopamine (DA) cells is central to generate the bursting activity, a phasic signal linked to DA‐related behaviours via the change in postsynaptic DA release. NMDARs are recruited during excitatory synaptic transmission by glutamate release, but the glycine site level of occupancy of these receptors during basal action potential‐dependent activity is not known for SNc DA neurons. We explored NMDAR‐dependent signals during exogenous applications of co‐agonists in midbrain slices from juvenile rats. We found that both glycine and D‐serine strengthened the NMDAR‐dependent component of excitatory postsynaptic currents (EPSCs) in a concentration‐dependent manner. EPSCs were also increased by endogenous glycine via the blockade of the glycine transport. The glycine site of NMDARs contributing to synaptic transmission is therefore subsaturated. The behaviourally relevant burst firing was more sensitive to exogenous D‐serine and endogenous glycine than to exogenous glycine. The mechanisms regulating the availability of the co‐agonists exert consequently a critical influence on the excitability of DA neurons via NMDARs. The modulation of the phasic firing in DA neurons by ambient NMDAR co‐agonists may be important for nigral information processing and downstream motor‐related behaviour.

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Astroglial Versus Neuronal D-Serine: Check Your Controls!

Cited by 46 publications

References 13 publications

Distinctive Roles of D-Amino Acids in the Homochiral World: Chirality of Amino Acids Modulates Mammalian Physiology and Pathology

Distinctive Roles of D-Amino Acids in the Homochiral World: Chirality of Amino Acids Modulates Mammalian Physiology and Pathology

Impact of Aging in Microglia-Mediated D-Serine Balance in the CNS

Subsaturation of the N‐methyl‐D‐aspartate receptor glycine site allows the regulation of bursting activity in juvenile rat nigral dopamine neurons

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