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The role of glutamate and its receptors in the proliferation, migration, differentiation and survival of neural progenitor cells

  • Neurology and Preclinical Neurological Studies - Review Article
  • Published:
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Abstract

The mammalian central nervous system derives from multipotent neural progenitor cells (NPCs) of the developing brain. During development the progenitor cells have enormous potential. They proliferate actively and differentiate into all the three main cell types, i.e., neurons, astrocytes and oligodendrocytes, of the adult brain through a tightly regulated process that coordinates cell proliferation, survival, migration, differentiation and apoptosis. This process is regulated by multiple extracellular signals including neurotrophic factors, chemoattractants and neurotransmitters in a coordinated manner. The main excitatory neurotransmitter glutamate is involved in promoting and/or inhibiting the proliferation, survival, migration and differentiation of NPCs acting via ionotropic or metabotropic receptors. The role of glutamate in the regulation of cortical NPCs has been most extensively studied. Glutamate appears to have a similar role in hippocampal, striatal as well as adult neural progenitors. Ionotropic α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate (KA) receptors and metabotropic glutamate receptor 5 (mGluR5) are expressed early during embryonic development as well as in the neurogenic zones of the adult brain. Ca2+-permeable AMPA/KA receptors are initially of importance for cell proliferation and neuronal motility. At later stages of development N-methyl-D-aspartate (NMDA) receptors have a more prominent role. MGluR5, which is the main metabotropic glutamate receptor during early development, is expressed in early progenitors and radial glial cells. Activation of this receptor promotes the proliferation and survival of NPCs. MGluR5 is involved in the extension of radial glial processes and in regulation of the migration of early cortical neurons.

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Abbreviations

ADAR:

Adenosine deaminase acting on RNA

AMPA:

α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid

BDNF:

Brain-derived neurotrophic factor

bFGF:

Basic fibroblast growth factor

cAMP:

Cyclic adenosine monophosphate

CNS:

Central nervous system

CP:

Cortical plate

DAG:

Diacylglycerol

DG:

Dentate gyrus

EGF:

Epidermal growth factor

GABA:

γ-Amino butyric acid

GFAP:

Glial fibrillary acidic protein

GLAST:

Glial glutamate-aspartate transporter

hNPC:

Human neural progenitor cell

iGluR:

Ionotropic glutamate receptor

IP3 :

1,4,5-Trisphosphate

IZ:

Intermediate zone

KA:

Kainate

LGE:

Lateral ganglionic eminence

MAP:

Microtubule-associated protein

mGluR:

Metabotropic glutamate receptor

MZ:

Marginal zone

NMDA:

N-Methyl-D-aspartate

NPC:

Neural progenitor cell

OB:

Olfactory bulb

PIP2 :

Phosphatidylinositol 4,5-biphosphate

PSA-NCAM:

Polysialylated neuronal cell adhesion molecule

RMS:

Rostral migratory stream

SGZ:

Subgranular zone

SP:

Subplate

SVZ:

Subventricular zone

TH:

Tyrosine hydroxylase

TRPC:

Canonical transient receptor potential

VZ:

Ventricular zone

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Acknowledgments

Our original research was supported by the Academy of Finland, the Sigrid Jusélius Foundation, the Magnus Ehrnrooth Foundation, the Finnish Medical Society, the Swedish Cultural Foundation in Finland, the University of Helsinki Funds, Medicinska Understödsföreningen Liv och Hälsa r.f., the Otto A. Malm Foundation, and the Waldemar von Frenckell’s Foundation.

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Correspondence to Karl E. Åkerman.

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Jansson, L.C., Åkerman, K.E. The role of glutamate and its receptors in the proliferation, migration, differentiation and survival of neural progenitor cells. J Neural Transm 121, 819–836 (2014). https://doi.org/10.1007/s00702-014-1174-6

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