Effect of glutamate receptor antagonists on migrating neural progenitor cells

Abstract

Neurotransmitters such as glutamate are potential regulators of neurogenesis. Interference with defined glutamate receptor subtypes affects proliferation, migration and differentiation of neural progenitor cells. The cellular targets for the actions of different glutamate receptor ligands are less well known. In this study we have combined calcium imaging, measurement of membrane potential, time-lapse imaging and immunocytochemistry to obtain a spatial overview of migrating mouse embryonic neural progenitor cell-derived cells responding to glutamate receptor agonists and antagonists. Responses via metabotropic glutamate receptor 5 correlated with radial glial cells and dominated in the inner migration zones close to the neurosphere. Block of metabotropic glutamate receptor 5 resulted in shorter radial glial processes, a transient increase in neuron-like cells emerging from the neurosphere and increased motility of neuron-like cells. α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors are present on the majority of migrating neuronal cells, which with time accumulate at the outer edge of the migration zone. Blocking these receptors leads to an enhanced extension of radial glial processes and a reduced motility of neuron-like cells. Our results indicate that functional glutamate receptors have profound effects on the motility of neural progenitor cells. The main target for metabotropic glutamate receptor 5 appears to be radial glial cells while AMPA/kainate receptors are mainly expressed in newborn neuronal cells and regulate the migratory progress of these cells. The results suggest that both metabotropic glutamate receptor 5 and AMPA/kainate receptors are of importance for the guidance of migrating embryonic progenitor cells.

Transient Receptor Potential Channels and Their Role in Modulating Radial Glial–Neuronal Interaction: A Signaling Pathway Involving mGluR5

“…2A, B) and cells treated with 1 mM pyr3 are shown in Fig. 2C and D. As shown previously [20,23], neuron-like cells exiting from the radial glial layer move in a phasic manner with fast bursts of rapid movement and intermittent stationary phases. During burst, the cells usually have a typical bipolar shape ( Fig.…”

“…1A). The expression pattern was similar in cells from the FVB mice strain (data not shown) used in previous studies [20,26]. Using RT-qPCR (normalized against proliferating cells), the mRNA expression for Trpc1 and Trpc3 was analyzed in cells from 3/6 DKO and 1/4/5 TKO mice.…”

“…BDNF, a neurotrophin, which stimulates cell migration and acts as a chemoattractant [32], also causes an increased motility index of the neuron-like cells [20]. In neurons, some of the effects of BDNF are mediated through activation of TRPC3 channels [5,6].…”

“…They are involved in activity-dependent forms of synaptic plasticity, both during development and in the adult life. The mGluR5 glutamate receptor is involved in neurogenesis [16][17][18][19] and appears to be expressed almost exclusively in radial glia in vitro migrating neurospherederived cells [20]. The similarity of the signaling mechanism involving mGluR5 and TrkB receptors might suggest that the developmental responses mediated through these receptors may also involve TRPC channels.…”

“…The similarity of the signaling mechanism involving mGluR5 and TrkB receptors might suggest that the developmental responses mediated through these receptors may also involve TRPC channels. Blocking of mGluR5 receptors significantly alters the motility pattern of migrating NPCs [20] and the mGluR5 calcium response displayed sensitivity to the TRPC3 blocker pyr3.…”