Inhibiting neuronal migration by blocking NMDA receptors in the embryonic rat cerebral cortex: a tissue culture study

Hirai, Kiyoshi; Yoshioka, Hiroshi; Kihara, Minako; Hasegawa, Kou; Sakamoto, Takako; Sawada, Tadashi; Fushiki, Shinji

doi:10.1016/s0165-3806(99)00019-x

Cited by 70 publications

(49 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NMDA receptors have been found to play a role in regulating cell migration, cell-cell adhesiveness, and apoptosis of developing neurons and glial cells (Balazs et al, 1989;Wang et al, 1996;Behar et al, 1999;Hirai et al, 1999). Hcys, by acting as an NMDA agonist at the glutamate-binding site, increases cerebellar neuron migration during development (Lipton et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…In vitro, the oligodendritic cells O-2A express NMDA receptors and NMDA receptor antagonists block O-2A cell migration (Wang et al, 1996). NMDA receptor antagonists (e.g., MK801ϩ) also block migration of cerebral cortical neurons in vitro (Behar et al, 1999;Hirai et al, 1999). Hcys can act as an agonist at the glutamate-binding site of NMDA receptors (Kim and Pae, 1996;Lipton et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of elevated homocysteine on cardiac neural crest migration in vitro

Brauer

Rosenquist

2002

Developmental Dynamics

View full text Add to dashboard Cite

A positive correlation between elevated maternal homocysteine (Hcys) and an increased risk of neural tube, craniofacial, and cardiac defects is well known. Studies suggest Hcys perturbs neural crest (NC) development and may involve N-methyl-D-aspartate (NMDA) receptors (Rosenquist et al., 1999). However, there is no direct evidence that Hcys alters NC cell behavior. Here, we evaluated the effect of Hcys on cardiac NC cell migratory behavior in vitro. Neural tube segments from chick embryos treated in ovo with or without Hcys were placed in culture and the migratory behavior of emigrating NC cells was monitored. Hcys significantly increased in vitro NC cell motility at all embryonic stages examined. NC cell surface area and perimeter were also increased. However, the relative distance NC cells migrated from their original starting point only increased in NC cells treated in ovo at stage 6 or at the time neural tube segments were cultured. Cysteine had no effect. NMDA mimicked Hcys' effect on NC motility and migration distance but had no effect on cell area or perimeter. The noncompetitive inhibitor of NMDA receptors, MK801؉, significantly inhibited NC cell motility, reduced migration distance, and also blocked the effects of NMDA and Hcys on NC motility and migratory distance in vitro. A monoclonal antibody directed against the NMDA receptor immunostained NC cells in vitro and, in western blots, bound a single protein with the appropriate molecular weight for the NMDA receptor in NC cell lysates. These data are consistent with the hypothesis that a Hcyssensitive NMDA-like receptor is expressed by early emigrating NC cells or their precursors, which is important in mediating their migratory behavior. Perturbation of this receptor may be related to some of the teratogenic effects observed with elevated Hcys.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of elevated homocysteine on cardiac neural crest migration in vitro

Brauer

Rosenquist

2002

Developmental Dynamics

View full text Add to dashboard Cite

show abstract

“…In the trailing process, by contrast, microtubule arrays are of mixed polarity. Thus, the extension of the leading process and translocation of the soma (nucleus and surrounding cytoplasm) within the membrane envelope may be orchestrated by a synchronized polymerization and disintegration of the microtubule that creates a rearrangement of the cytoskeletal scaffolding (Rivas and Hatten, 1995;Rakic et al, 1996;Feng et al, 2004;Schaar and McConnell, 2005;Xie et al, 2006) that is regulated by Calcium fluxes through the activity of various receptor/channel complexes (e.g., Komuro and Rakic, 1993;Behar et al, 1999;Hirai et al, 1999;Haydar et al, 2000, Owen andKriegstein, 2002). Synergistic action of other molecular pathways may be involved in cytoskeletal rearrangement, such as Doublecortin and MEKK 4, which is important for mobilization of another cytoskeletal protein, Filamin (Sarkisian et al, 2006).…”

Section: Nuclear and Somal Translocationmentioning

confidence: 99%

The radial edifice of cortical architecture: From neuronal silhouettes to genetic engineering

Rakić

2007

Brain Research Reviews

230

185

View full text Add to dashboard Cite

The developmental principles that establish the columnar edifice of the cerebral cortex underlie its evolution and dictate its physiological operations and cognitive capacity. This article contrasts the initial discoveries made by Ramón y Cajal and his contemporaries, based on the ingenious interpretation of neuronal shapes and their relationships using the Golgi method, with new insights based on the application of the most advanced methods of molecular biology and genetics. We can now propose a realistic model of how the sequence of gene expression, cascade of multiple molecular pathways and cell-cell interactions establish the number of neurons, guide their migration and allocation into proper regions and determine their differentiation into specific phenotypes that establish specific synaptic connections. The findings obtained from different levels of analyses sustain the radial unit hypothesis as a useful framework for understanding the mechanisms of cortical development and its evolution as an organ of thought.

show abstract

“…Evidence came first from imaging studies of granule cell migration in acute mouse cerebellar slices, in which blockade or enhancement of Ca 2+ influx through N-type Voltage Dependent Calcium Channels (VDCCs) or the NMDAR reduced or promoted the rate of granule cell movement, respectively [10,15]. Similarly, the involvement of calcium influx from the extracellular medium has also been reported for the migration of other cell types like GNRH-1 neurons, cortical projection neurons and interneurons [13,16-18]. …”

Section: Introductionmentioning

confidence: 99%

Neuregulin1/ErbB4-induced migration in ST14A striatal progenitors: calcium-dependent mechanisms and modulation by NMDA receptor activation

et al. 2011

View full text Add to dashboard Cite

BackgroundA number of studies have separately shown that the neuregulin1 (NRG1)/ErbB4 system and NMDA-type glutamate receptors (NMDARs) are involved in several aspects of neuronal migration. In addition, intracellular calcium fluctuations play central roles in neuronal motility. Stable expression of the tyrosine kinase receptor ErbB4 promotes migratory activity in the neural progenitor cell line ST14A upon NRG1 stimulation. In this work we analyzed the potential interactions between the NRG1/ErbB4 system and NMDARs in the ST14A migratory process as well as its calcium dependence.ResultsRT-PCR studies have shown that both native ST14A cells (non-expressing ErbB4), as well as ErbB4-transfected cells express low levels of a restricted number of NMDAR subunits: NR1, NR2C, NR2D and NR3B. The resulting NMDAR would form Ca2+ channels characterized by low Mg2+-sensitivity and low Ca2+-permeability, generating small, long-lasting currents. Ca2+-imaging experiments showed slow [Ca2+]i increases in 45% of the cells following 8 μM NMDA stimulation. Basal migration of ErbB4-transfected ST14A cells was unaffected by 18 hrs NMDA incubation. However, over the same incubation time, NMDA was able to significantly enhance NRG1-induced migration. Pre-incubation with the intracellular calcium chelator BAPTA-AM reduced both NRG1- and NRG1/NMDA-stimulated migration, suggesting the involvement of Ca2+ in these processes. NRG1 stimulation of ErbB4-transfected ST14A cells induced a sustained, long-lasting increase in [Ca2+]i, in 99% of the cells. These intracellular Ca2+ signals could be ascribed to both release from intracellular stores and influx from the extracellular medium trough a mechanism of store-operated calcium entry (SOCE). Short-time co-incubation of NMDA and NRG1 did not substantially modify the NRG1-induced intracellular calcium signals.ConclusionsIn summary, NRG1 stimulation of the ErbB4 receptor exerts a sustained [Ca2+]i increase in ST14A neural progenitors; NRG1-induced migration is Ca2+-dependent and can be positively modulated by activation of the NMDA receptor.

show abstract

Inhibiting neuronal migration by blocking NMDA receptors in the embryonic rat cerebral cortex: a tissue culture study

Cited by 70 publications

References 13 publications

Effect of elevated homocysteine on cardiac neural crest migration in vitro

Effect of elevated homocysteine on cardiac neural crest migration in vitro

The radial edifice of cortical architecture: From neuronal silhouettes to genetic engineering

Neuregulin1/ErbB4-induced migration in ST14A striatal progenitors: calcium-dependent mechanisms and modulation by NMDA receptor activation

Contact Info

Product

Resources

About