Enhanced astrocytic d-serine underlies synaptic damage after traumatic brain injury

Perez, Enmanuel J.; Tapanes, Stephen A.; Loris, Zachary B.; Balu, Darrick T.; Sick, Thomas J.; Coyle, Joseph T.; Liebl, Daniel J.

doi:10.1172/jci92300

Cited by 101 publications

(116 citation statements)

References 59 publications

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“…Reactive astrocytes typically proliferate after brain insults, such as traumatic brain injury (TBI). Hippocampal TBI was shown to cause proliferation of SR‐expressing reactive astrocytes over 7 days while neuronal SR in injured neurons declined . Notably, silencing the expression of SR in astrocytes by conditional srr inactivation only in astrocytes prevented the electrophysiologic and cognitive deficits after TBI.…”

Section: Pathophysiological Role Of Serine Racemase and D‐serinesupporting

confidence: 73%

Glutamate hypothesis in schizophrenia

Uno

Coyle

2019

Psychiatry Clin Neurosci

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248

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Schizophrenia is a chronic and severe psychiatric disorder that has profound impact on an individual’s life and on society. Thus, developing more effective therapeutic interventions is essential. Over the past quarter‐century, an abundance of evidence from pharmacologic challenges, post‐mortem studies, brain imaging, and genetic studies supports the role of glutamatergic dysregulation in the pathophysiology of schizophrenia, and the results of recent randomized clinical trials based on this evidence have yielded promising results. In this article, we review the evidence that alterations in glutamatergic neurotransmission, especially focusing on the N‐methyl‐d‐aspartate receptor (NMDAR) function, may be a critical causative feature of schizophrenia, how this contributes to pathologic circuit function in the brain, and how these insights are revealing whole new avenues for treatment development that could reduce treatment‐resistant symptoms, which account for persistent disability.

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Section: Pathophysiological Role Of Serine Racemase and D‐serinesupporting

confidence: 73%

Glutamate hypothesis in schizophrenia

Uno

Coyle

2019

Psychiatry Clin Neurosci

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248

172

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“…Indeed, several commercial (Sarissa Biomedical Ltd, Coventry, UK) or home-made D-serine biosensors are based on the use of DAAO from the yeast Rhodotorula gracilis (RgDAAO) layered on an electroconductive support. 3,24,54 But the response of these assays is nonlinear with D-serine concentration. 53 RgDAAO catalyzes the oxidative deamination of neutral D-AAs 53,54 and does not act either on glycine (K m = 160 mmol/L, ie, two to three orders of magnitude higher than the physiological concentration), or on D-aspartate and D-glutamate (k cat ≤ 1 per second vs. 61 per second for D-serine), known to act also on NMDAR.…”

Section: Detecting or Not Detecting D -Serine Properly With Analytimentioning

confidence: 99%

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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“…However, traumatic brain injury (TBI) causes reactive astrocytes to proliferate in the hippocampus. It is in these reactive astrocytes that SR can be easily detected using immunohistochemistry [8]. Furthermore, the TBI-induced cognitive impairments are reversed by selectively eliminating SR in GFAP-expressing astrocytes in adulthood before injury [8].…”

mentioning

confidence: 99%

“…It is in these reactive astrocytes that SR can be easily detected using immunohistochemistry [8]. Furthermore, the TBI-induced cognitive impairments are reversed by selectively eliminating SR in GFAP-expressing astrocytes in adulthood before injury [8]. Therefore, astrocytic SR appears to play a role in pathology where reactive astrocytes are present, but not in quiescent astrocytes that are present in normal brain.…”

mentioning

confidence: 99%