SDF‐1α‐mediated modulation of synaptic transmission in rat cerebellum

Limatola, Cristina; Giovannelli, Alessandro; Maggi, Laura; Ragozzino, Davide; Castellani, Loriana; Ciotti, Maria Teresa; Vacca, Fabrizio; Mercanti, Delio; Santoni, Angela; Eusebi, Fabrizio

doi:10.1046/j.1460-9568.2000.00139.x

Cited by 122 publications

(103 citation statements)

References 39 publications

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“…Several studies have recently suggested that, beyond their classical involvement in neuroinflammatory and infectious processes, chemokines may play additional roles in the CNS, such as regulation of neuronal survival, differentiation, synaptic transmission, and plasticity (Meucci et al, 1998;Asensio and Campbell, 1999;Limatola et al, 2000;Bezzi et al, 2001;Lu et al, 2002;Stumm et al, 2002). In analogy to what is observed in hematopoietic cells (Broxmeyer et al, 2001), emerging data indicate that SDF-1μ can regulate proliferation and maturation of developing neurons (Zou et al, 1998;Klein et al, 2001;Lu et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

The Chemokine Receptor CXCR4 Regulates Cell-Cycle Proteins in Neurons

Khan

Brandimarti

Musser

et al. 2003

J. of Neurovirology

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Neurons express a variety of chemokine receptors that regulate neuronal signaling and survival, including CXCR4 and CCR5, the two major human immunodeficiency virus (HIV) coreceptors. However, the role of chemokine receptors in HIV neuropathology and neuroinflammatory disorders is still unclear. This study aims to determine whether chemokine receptors regulate the activity of cell-cycle proteins in neurons and evaluate the possibility that alterations of these proteins are involved in HIV neuropathogenesis. The authors studied the effect of the chemokine stromal cellderived factor (SDF)-1α, the natural CXCR4 ligand, and an X4-using variant of gp120 on the activity of cell-cycle proteins involved in neuronal apoptosis and differentiation, such as Rb and E2F-1. Changes in expression, localization, and phosphorylation/activation of Rb and E2F-1 induced by SDF-1α (20 nM) gp120 IIIB (200 pM) were analyzed in primary cultures of rat neurons and in a human cell line expressing recombinant CXCR4. The data indicate that changes in the nuclear and cytosolic levels of Rb-which result in the functional loss of this protein-are associated with apoptosis in hippocampal or cerebellar granule neurons and in cell lines. SDF-1α, which is able to rescue these neurons from apoptosis, induces a time-dependent increase of total Rb expression while decreasing the nuclear content of phosphorylated (Ser780/Ser795) Rb and the transcriptional activity of E2F-1. The HIV envelope protein gp120 IIIB exerts opposite effects at the nuclear level. These data indicate that CXCR4 affects cell-cycle proteins in neurons and raise the possibility that chemokines may contribute to neuronal survival by repressing the activity of E2F-dependent apoptotic genes and maintaining neurons in a highly differentiated and quiescent state. This state may be altered during neuroinflammatory conditions and/or by HIV-derived proteins.

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Section: Discussionmentioning

confidence: 99%

The Chemokine Receptor CXCR4 Regulates Cell-Cycle Proteins in Neurons

Khan

Brandimarti

Musser

et al. 2003

J. of Neurovirology

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“…Limatola C et al (2000) first reported that Purkinje neurons in cerebellar slices responded to CXCL12 application by a slow inward current followed by an increase of both intracellular Ca 2+ and spontaneous synaptic activity. The same group reported that the amplitude of evoked excitatory postsynaptic currents (EPSC) of Purkinje neurons was reversibly reduced by CXCL12 application (Ragozzino D et al, 2002).…”

Section: Neuromodulationmentioning

confidence: 99%

Multiple roles of chemokine CXCL12 in the central nervous system: A migration from immunology to neurobiology

Ransohoff

2008

Progress in Neurobiology

303

245

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Chemotactic cytokines (chemokines) have been traditionally defined as small (10-14 kDa) secreted leukocyte chemoattractants. However, chemokines and their cognate receptors are constitutively expressed in the central nervous system (CNS) where immune activities are under stringent control. Why and how the CNS uses the chemokine system to carry out its complex physiological functions has intrigued neurobiologists. Here, we focus on chemokine CXCL12 and its receptor CXCR4 that have been widely characterized in peripheral tissues and delineate their main functions in the CNS. Extensive evidence supports CXCL12 as a key regulator for early development of the CNS. CXCR4 signaling is required for the migration of neuronal precursors, axon guidance/pathfinding and maintenance of neural progenitor cells (NPCs). In the mature CNS, CXCL12 modulates neurotransmission, neurotoxicity and neuroglial interactions. Thus, chemokines represent an inherent system that helps establish and maintain CNS homeostasis. In addition, growing evidence implicates altered expression of CXCL12 and CXCR4 in the pathogenesis of CNS disorders such as HIVassociated encephalopathy, brain tumor, stroke and multiple sclerosis (MS), making them the plausible targets for future pharmacological intervention.

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“…Several studies have demonstrated that chemokines CXCL1, CXCL8, or CXCL12 regulate neurotransmitter release or modulate ion channel activity at both the presynaptic and postsynaptic levels. 36,37 Moreover, a recent study has reported that CX3CL1, a chemokine constitutively expressed in the CNS (along with CXCL12 and CXCL14), is a potent neuromodulator of evoked excitatory synaptic transmission. 38 Beyond their role in the CNS under physiological conditions, chemokines and chemokine receptors are studied primarily as mediators of CNS pathologies, especially those with an inflammatory component such as multiple sclerosis (MS).…”

Section: Chemokines and Chemokine Receptors In The Central Nervous Symentioning

confidence: 99%

Chemokines and Chemokine Receptors in Neurological Disease: Raise, Retain, or Reduce?

Savarin-Vuaillat¹,

Ransohoff²

2007

Neurotherapeutics

155

126

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Summary:Chemokines and chemokine receptors comprise a large number of molecules implicated in a wide range of physiological and pathological functions. Numerous studies have demonstrated the roles of chemokines and chemokine receptors: 1) during development, by regulating hematopoiesis, cardiogenesis, and vascular and cerebellar development; 2) during tumor biology, by controlling cell proliferation, angiogenesis, and metastasis; and 3), especially during leukocyte migration, by acting on firm adhesion, locomotion, diapedesis, and chemotaxis. This review focuses on chemokine and chemokine receptor involvement in diverse neurological diseases and their therapeutic potentials. Because of its induction or upregulation during CNS pathologies, members of the chemokine system can be used as biological markers. CXCR4 and CXCL12, by the correlation between their expression and the glioblastoma tumor progression, could be a marker to grade this type of CNS tumor. CCR1, by virtue of specific expression in A␤ plaques, may be a marker for Alzheimer pathology. Downregulation of CCL2 in cerebrospinal fluid may be a candidate to characterize multiple sclerosis (MS), but needs additional investigation. Moreover, chemokines and chemokine receptors represent interesting therapeutic targets. Using chemokine receptor antagonists, several studies provided exciting findings for potential neurological disease treatment. Chemokine receptor antagonists reduce disease severity in animal models of MS. In glioblastoma, a CXCR4 antagonist (AMD3100) showed an inhibition of tumor growth. Inhibition of chemokine receptor signaling is not the only therapeutic strategy: for example, CXCR4 -CXCL12 has anti-inflammatory properties and CX3CL1-CX3CR1 controls neurotoxicity. Thus, chemokine biology suggests several approaches for treating neurological disease.

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SDF‐1α‐mediated modulation of synaptic transmission in rat cerebellum

Cited by 122 publications

References 39 publications

The Chemokine Receptor CXCR4 Regulates Cell-Cycle Proteins in Neurons

The Chemokine Receptor CXCR4 Regulates Cell-Cycle Proteins in Neurons

Multiple roles of chemokine CXCL12 in the central nervous system: A migration from immunology to neurobiology

Chemokines and Chemokine Receptors in Neurological Disease: Raise, Retain, or Reduce?

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