N-Methyl-D-Aspartate Receptors in Hematopoietic Cells: What Have We Learned?

Kalev‐Zylinska, Maggie L.; Hearn, James I.; Makhro, Asya; Bogdanova, Anna

doi:10.3389/fphys.2020.00577

Cited by 10 publications

(9 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, NMDA receptors in mature erythrocytes may affect the life span of erythrocytes. In mature human and rat erythrocytes, NMDA receptors impact cellular nitric oxide synthase activity [ 9 , 20 ]. It is possible that altered NMDA receptor function affects the life span of erythrocytes.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…On the other hand, recent studies revealed that NMDA receptors play significant roles in hematopoiesis [ 9 ]. NMDA receptor subunits are expressed in megakaryocytes and erythroid cells and function as ion channels, similar to their neuronal counterparts [ 9 ]. NMDAR1 deficiency impairs differentiation of megakaryocytic-erythroid progenitor (MEP)-like leukemia cells (Meg-01 cells) [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…NMDAR1 deficiency impairs differentiation of megakaryocytic-erythroid progenitor (MEP)-like leukemia cells (Meg-01 cells) [ 10 ]. It is proposed that the NMDA receptors balance both megakaryocytic and erythroid cell fates at the level of a bipotential MEP [ 9 ]. These facts attract our attention to the functional relationship between Lrfn2 and NMDA receptors in hematopoiesis.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Dysregulation of erythropoiesis and altered erythroblastic NMDA receptor-mediated calcium influx in Lrfn2-deficient mice

et al. 2021

View full text Add to dashboard Cite

LRFN2 encodes a synaptic adhesion-like molecule that physically interacts with N-methyl-D-aspartate (NMDA) receptor 1 and its scaffold proteins. Previous studies in humans and mice have demonstrated its genetic association with neurodevelopmental disorders such as learning deficiency and autism. In this study, we showed that Lrfn2-deficient (KO) mice exhibit abnormalities of erythropoietic systems due to altered NMDA receptor function. In mature Lrfn2 KO male mice, peripheral blood tests showed multilineage abnormalities, including normocytic erythrocythemia, and reduced platelet volume. Colony forming unit assay using bone marrow cells revealed decreases in the counts of erythrocyte progenitors (CFU-E) as well as granulocytes and monocyte progenitors (CFU-GM). Whole bone marrow cell staining showed that serum erythropoietin (EPO) level was decreased and EPO receptor-like immunoreactivity was increased. Flow cytometry analysis of bone marrow cells revealed increased early erythroblast count and increased transferrin receptor expression in late erythroblasts. Further, we found that late erythroblasts in Lrfn2 KO exhibited defective NMDA receptor-mediated calcium influx, which was inhibited by the NMDA receptor antagonist MK801. These results indicate that Lrfn2 has biphasic roles in hematopoiesis and is associated with the functional integrity of NMDA receptors in hematopoietic cells. Furthermore, taken together with previous studies that showed the involvement of NMDA receptors in hematopoiesis, the results of this study indicate that Lrfn2 may regulate erythropoiesis through its regulatory activity on NMDA receptors.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dysregulation of erythropoiesis and altered erythroblastic NMDA receptor-mediated calcium influx in Lrfn2-deficient mice

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In addition to cilia-associated genes, the most significant variable in our model was a region of GRIN2C, an NMDA receptor that may have effects on hematopoietic differentiation by controlling calcium homeostasis in differentiating cells [81] , [82] . Although the full structure and function of this gene has yet to be elucidated, we identified a narrow 50-basepair region in GRIN2C’s N-terminal extracellular domain that is significantly associated with accelerated relapse in high-risk pediatric B-ALL patients.…”

Section: Discussionmentioning

confidence: 99%

Random survival forest model identifies novel biomarkers of event-free survival in high-risk pediatric acute lymphoblastic leukemia

Bohannan

Coffman

Mitrofanova

2022

Computational and Structural Biotechnology Journal

View full text Add to dashboard Cite

show abstract

A pilot clinical phase II trial MemSID: Acute and durable changes of red blood cells of sickle cell disease patients on memantine treatment

Mahkro

Hegemann

Seiler

et al. 2020

eJHaem

Self Cite

View full text Add to dashboard Cite

An increase in abundance and activity of N‐methyl D‐aspartate receptors (NMDAR) was previously reported for red blood cells (RBCs) of sickle cell disease (SCD) patients. Increased Ca2+ uptake through the receptor supported dehydration and RBC damage. In a pilot phase IIa‐b clinical trial MemSID, memantine, a blocker of NMDAR, was used for treatment of four patients for 12 months. Two more patients that have enrolled into the study did not finish it. One of them had psychotic event following the involuntary overdose of the drug, whereas the other had vertigo and could not comply to the trial visits schedule. Acute and durable responses of RBCs of SCD patients to daily oral administration of memantine were monitored. Markers of RBC turnover, changes in cell density, and alterations in ion handling and RBC morphology were assessed. Acute transient shifts in intracellular Ca2+, volume and density, and reduction in plasma lactate dehydrogenate activity were observed already within the first month of treatment. Durable effects of memantine included (a) decrease in reticulocyte counts, (b) reduction in reticulocyte hemoglobinization, (c) advanced membrane maturation and its stabilization as follows from reduction in the number of NMDAR per cell and reduction in hemolysis, and (iv) rehydration and decrease in K+ leakage from patients’ RBC. Memantine therapy resulted in reduction in number of cells with sickle morphology that was sustained at least over 2 months after therapy was stopped indicating an improvement in RBC longevity.

show abstract

N-Methyl-D-Aspartate Receptors in Hematopoietic Cells: What Have We Learned?

Abstract: also contributed to the review process for this manuscript.

Cited by 10 publications

References 87 publications

Dysregulation of erythropoiesis and altered erythroblastic NMDA receptor-mediated calcium influx in Lrfn2-deficient mice

Dysregulation of erythropoiesis and altered erythroblastic NMDA receptor-mediated calcium influx in Lrfn2-deficient mice

Random survival forest model identifies novel biomarkers of event-free survival in high-risk pediatric acute lymphoblastic leukemia

A pilot clinical phase II trial MemSID: Acute and durable changes of red blood cells of sickle cell disease patients on memantine treatment

Contact Info

Product

Resources

About