The Chemokine Stromal Cell-Derived Factor-1 Regulates GABAergic Inputs to Neural Progenitors in the Postnatal Dentate Gyrus

Abstract

Stromal cell-derived factor-1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) are important regulators of the development of the dentate gyrus (DG). Both SDF-1 and CXCR4 are also highly expressed in the adult DG. We observed that CXCR4 receptors were expressed by dividing neural progenitor cells located in the subgranular zone (SGZ) as well as their derivatives including doublecortinexpressing neuroblasts and immature granule cells. SDF-1 was located in DG neurons and in endothelial cells associated with DG blood vessels. SDF-1-expressing neurons included parvalbumin-containing GABAergic interneurons known as basket cells. Using transgenic mice expressing an SDF-1-mRFP1 (monomeric red fluorescence protein 1) fusion protein we observed that SDF-1 was localized in synaptic vesicles in the terminals of basket cells together with GABA-containing vesicles. These terminals were often observed to be in close proximity to dividing nestin-expressing neural progenitors in the SGZ. Electrophysiological recordings from slices of the DG demonstrated that neural progenitors received both tonic and phasic GABAergic inputs and that SDF-1 enhanced GABAergic transmission, probably by a postsynaptic mechanism. We also demonstrated that, like GABA, SDF-1 was tonically released in the DG and that GABAergic transmission was partially dependent on coreleased SDF-1. These data demonstrate that SDF-1 plays a novel role as a neurotransmitter in the DG and regulates the strength of GABAergic inputs to the pool of dividing neural progenitors. Hence, SDF-1/ CXCR4 signaling is likely to be an important regulator of adult neurogenesis in the DG.

Murine adult neural progenitor cells alter their proliferative behavior and gene expression after the activation of toll-like-receptor 3

“…Finally, the development of new generated neurons crucially depends on CXCL12, as it modulates axon growth and synapse formation by signaling through CXCR4. This signaling leads to the regulation of GABAergic inputs to NPCs from mature granule cells, thereby supporting the maturation of young neurons [46,47]. According to previous observations, our findings confirmed the expression of CXCR4 mRNA and the absence of CXCL12 mRNA in cultured NPCs.…”

Inhibition of CXCL12 Signaling Attenuates the Postischemic Immune Response and Improves Functional Recovery after Stroke

“…35 Further studies are required to determine the extent to which different CXCL12 isoforms contribute to the mechanisms of neuronal plasticity during reorganization of the ischemic hemisphere. Recently, it was demonstrated that CXCL12 affects the function of GABAergic neurons at the infarct boundary 39 and upregulation of CXCL12 in glial cells promotes differentiation of oligodendrocyte precursor cells, which are important for remyelination in the ischemic hemisphere. 40 While these potentially beneficial long-term processes require the activation of the CXCL12 pathway, our results show that immoderate excessive activation during the first week is detrimental for recovery of function after stroke supporting a dual role of this pathway after stroke.…”

The extracellular matrix glycoprotein tenascin-R regulates neurogenesis during development and in the adult dentate gyrus of mice

“…Although the signaling mechanisms that regulate neurogenesis in the adult dentate gyrus have remained largely unknown, increasing evidence indicates that the proliferation and differentiation of NSCs in the dentate gyrus are influenced by neurotransmitters. Importantly, NSCs in the dentate gyrus receive GABAergic input (Bhattacharyya et al, 2008) that promotes their differentiation into neurons (Tozuka et al, 2005). Furthermore, GABAergic signaling decreases the proliferation of NSCs in the subventricular zone of the adult brain (Liu et al, 2005).…”