Endogenous activation of metabotropic glutamate receptors supports the proliferation and survival of neural progenitor cells

Giorgi-Gerevini, V. Di; Melchiorri, Daniela; Battaglia, Giuseppe; Ricci–Vitiani, Lucia; Ciceroni, C.; Busceti, Carla L.; Biagioni, Francesca; Iacovelli, Luisa; Canudas, Anna Maria; Parati, Eugenio; Maria, Ruggero De; Nicoletti, Ferdinando

doi:10.1038/sj.cdd.4401639

Cited by 124 publications

(124 citation statements)

References 47 publications

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“…Di Giorgi-Gerevini et al (2005) reported that adult mice lacking mGluR5 or treated with mGluR5 antagonists showed a dramatic reduction in the number of proliferating cells in the SVZ (Giorgi-Gerevini et al, 2005). This in vivo study shows that mGluR5 are tonically activated by ambient glutamate suggesting a local source of glutamate in the SVZ consistent with our strong immunoreactivity in SVZ astrocytes (see Fig.…”

Section: Glutamate: a Positive Regulator Of Adult Neurogenesissupporting

confidence: 75%

GABA and glutamate signaling: homeostatic control of adult forebrain neurogenesis

2007

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SummaryThe neurotransmitter GABA exerts a strong negative influence on the production of adult-born olfactory bulb interneurons via tightly regulated, non-synaptic GABAergic signaling. After discussing some findings on GABAergic signaling in the neurogenic subventricular zone (SVZ), we provide data suggesting ambient GABA clearance via two GABA transporter subtypes and further support for a non-vesicular mechanism of GABA release from neuroblasts. While GABA works in cooperation with the neurotransmitter glutamate during embryonic cortical development, the role of glutamate in adult forebrain neurogenesis remains obscure. Only one of the eight metabotropic glutamate receptors (mGluRs), mGluR5, has been reported to tonically increase the number of proliferative SVZ cells in vivo, suggesting a local source of glutamate in the SVZ. We show here that glutamate antibodies strongly label subventricular zone (SVZ) astrocytes, some of which are stem cells. We also show that some SVZ neuroblasts express one of the ionotropic glutamate receptors, AMPA/kainate receptors, earlier than previously thought. Collectively, these findings suggest that neuroblast-to-astrocyte GABAergic signaling may cooperate with astrocyte-toneuroblast glutamatergic signaling to provide strong homeostatic control on the production of adultborn olfactory bulb interneurons.

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Section: Glutamate: a Positive Regulator Of Adult Neurogenesissupporting

confidence: 75%

GABA and glutamate signaling: homeostatic control of adult forebrain neurogenesis

2007

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“…Di Giorgi-Gerevini et al (2005) reported that adult mice lacking mGluR5 or treated with mGluR5 antagonists showed a dramatic reduction in the number of proliferating cells in the SVZ (Giorgi-Gerevini et al 2005). This in vivo study shows that mGluR5 are tonically activated by ambient glutamate suggesting a local source of glutamate in the SVZ consistent with our strong immunoreactivity in SVZ astrocytes (see Fig.…”

Section: Glutamate: a Positive Regulator Of Adult Neurogenesissupporting

confidence: 77%

GABA and glutamate signaling: homeostatic control of adult forebrain neurogenesis

2007

View full text Add to dashboard Cite

The neurotransmitter GABA exerts a strong negative influence on the production of adult-born olfactory bulb interneurons via tightly regulated, non-synaptic GABAergic signaling. After discussing some findings on GABAergic signaling in the neurogenic subventricular zone (SVZ), we provide data suggesting ambient GABA clearance via two GABA transporter subtypes and further support for a non-vesicular mechanism of GABA release from neuroblasts. While GABA works in cooperation with the neurotransmitter glutamate during embryonic cortical development, the role of glutamate in adult forebrain neurogenesis remains obscure. Only one of the eight metabotropic glutamate receptors (mGluRs), mGluR5, has been reported to tonically increase the number of proliferative SVZ cells in vivo, suggesting a local source of glutamate in the SVZ. We show here that glutamate antibodies strongly label subventricular zone (SVZ) astrocytes, some of which are stem cells. We also show that some SVZ neuroblasts express one of the ionotropic glutamate receptors, AMPA/kainate receptors, earlier than previously thought. Collectively, these findings suggest that neuroblast-to-astrocyte GABAergic signaling may cooperate with astrocyte-to-neuroblast glutamatergic signaling to provide strong homeostatic control on the production of adult-born olfactory bulb interneurons.

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“…However, the in vivo effect of glutamate on neurogenesis remains incompletely understood. Glutamate has been suggested to be beneficial for neurogenesis [22][23][24], but studies on different anatomical regions in the mammalian brain and with different experimental approaches yielded discrepant results [18]: a low dose of glutamate (50 mM) applied to mouse brain slice culture increased cell proliferation in the ventricular zone, but decreased cell proliferation in the subventricular zone [24]. However, a high dose of glutamate (300 mM) applied to brain slice culture decreased cell proliferation and survival in the ventricular zone [25].…”

Section: Introductionmentioning

confidence: 99%

Glutaminase 1 Is Essential for the Differentiation, Proliferation, and Survival of Human Neural Progenitor Cells

Wang

Huang²,

Zhao

et al. 2014

Stem Cells and Development

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Glutaminase is the enzyme that converts glutamine into glutamate, which serves as a key excitatory neurotransmitter and one of the energy providers for cellular metabolism. Previous studies have revealed that mice lacking glutaminase 1 (GLS1), the dominant isoform in the brain and kidney, died shortly after birth due to disrupted glutamatergic transmission, suggesting the critical role of GLS1 in the physiological functions of synaptic network. However, whether GLS1 regulates neurogenesis, a process by which neurons are generated from neural progenitor cells (NPCs), is unknown. Using a human NPC model, we found that both GLS1 isotypes, kidney-type glutaminase and glutaminase C, were upregulated during neuronal differentiation, which were correlated with the expression of neuronal marker microtubule-associated protein 2 (MAP-2). To study the functional impact of GLS1 on neurogenesis, we used small interference RNA targeting GLS1 and determined the expressions of neuronal genes by western blot, real-time polymerase chain reaction, and immunocytochemistry. siRNA silencing of GLS1 significantly reduced the expression of MAP-2, indicating that GLS1 is essential for neurogenesis. To unravel the specific process(es) of neurogenesis being affected, we further studied the proliferation and survival of NPCs in vitro. siRNA silencing of GLS1 significantly reduced the Ki67 + and increased the TUNEL + cells, suggesting critical roles of GLS1 for the proliferation and survival of NPCs. Together, these data suggest that GLS1 is critical for proper functions of NPCs, including neuronal differentiation, proliferation, and survival.

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Endogenous activation of metabotropic glutamate receptors supports the proliferation and survival of neural progenitor cells

Cited by 124 publications

References 47 publications

GABA and glutamate signaling: homeostatic control of adult forebrain neurogenesis

GABA and glutamate signaling: homeostatic control of adult forebrain neurogenesis

GABA and glutamate signaling: homeostatic control of adult forebrain neurogenesis

Glutaminase 1 Is Essential for the Differentiation, Proliferation, and Survival of Human Neural Progenitor Cells

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