Knockdown of the CXCL12/CXCR7 chemokine pathway results in learning deficits and neural progenitor maturation impairment in mice

Trousse, Françoise; Jemli, Achraf; Silhol, Michelle; Garrido, Elisabeth; Crouzier, Lucie; Naert, Gaëlle; Maurice, Tangui; Rossel, Mireille

doi:10.1016/j.bbi.2019.05.019

Cited by 10 publications

(8 citation statements)

References 51 publications

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“…Odemis et al found that CXCR7 was expressed on the surface of astrocytes in the CNS [ 50 ]. However, some studies found that CXCR7 was expressed in both astrocytes and microglia [ 51 ]. CXCR7 promotes cell maturation, differentiation, polarization, and migration when combined with its ligand CXCL12 [ 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Microglia induce the transformation of A1/A2 reactive astrocytes via the CXCR7/PI3K/Akt pathway in chronic post-surgical pain

Liu

Chen

et al. 2020

J Neuroinflammation

126

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Background: Activated astrocytes play important roles in chronic post-surgical pain (CPSP). Recent studies have shown reactive astrocytes are classified into A1 and A2 phenotypes, but their precise roles in CPSP remain unknown. In this study, we investigated the roles of spinal cord A1 and A2 astrocytes and related mechanisms in CPSP. Methods: We used a skin/muscle incision and retraction (SMIR) model to establish a rat CPSP model. Microglia, CXCR7, and the phosphoinositide 3-kinase/Akt (PI3K/Akt) signaling pathways were regulated by intrathecal injections of minocycline (a non-specific microglial inhibitor), AMD3100 (a CXCR7 agonist), and LY294002 (a specific PI3K inhibitor), respectively. Mechanical allodynia was detected with von Frey filaments. The changes in microglia, A1 astrocytes, A2 astrocytes, CXCR7, and PI3K/Akt signaling pathways were examined by enzyme-linked immunosorbent assay (ELISA), western blot, and immunofluorescence. Results: Microglia were found to be activated, with an increase in interleukin-1 alpha (IL-1α), tumor necrosis factor alpha (TNFα), and complement component 1q (C1q) in the spinal cord at an early stage after SMIR. On day 14 after SMIR, spinal cord astrocytes were also activated; these were mainly of the A1 phenotype and less of the A2 phenotype. Intrathecal injection of minocycline relieved SMIR-induced mechanical allodynia and reverted the ratio of A1/A2 reactive astrocytes. The expression of CXCR7 and PI3K/Akt signaling was decreased after SMIR, while they were increased after treatment with minocycline. Furthermore, intrathecal injection of AMD3100 also relieved SMIR-induced mechanical allodynia, reverted the ratio of A1/A2 reactive astrocytes, and activated the PI3K/Akt signaling pathway, similar to the effects produced by minocycline. However, intrathecal injection of AMD3100 did not increase the analgesic effect of minocycline. Last, LY294002 inhibited the analgesic effect and A1/A2 transformation induced by minocycline and AMD3100 after SMIR. Conclusion: Our results indicated that microglia induce the transformation of astrocytes to the A1 phenotype in the spinal cord via downregulation of the CXCR7/PI3K/Akt signaling pathway during CPSP. Reverting A1 reactive astrocytes to A2 may represent a new strategy for preventing CPSP.

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Section: Discussionmentioning

confidence: 99%

Microglia induce the transformation of A1/A2 reactive astrocytes via the CXCR7/PI3K/Akt pathway in chronic post-surgical pain

Liu

Chen

et al. 2020

J Neuroinflammation

126

View full text Add to dashboard Cite

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“…Other authors documented the importance of chemokines in synaptic transmission, plasticity and spatial memory [ 34 - 36 ]. A continuously increasing number of reports indicate that in the CNS these molecules also take part in adult neurogenesis [ 37 , 38 ], gene regulation and abnormal neural stem cell maturation [ 39 ], cell proliferation [ 40 ], neuroendocrine regulation (reviewed by Callewaere et al [ 41 ]), neurotransmission [ 42 ] and neuroprotection [ 43 ].…”

Section: Chemokines and Clusters Of Differentiation In The Healthy Brmentioning

confidence: 99%

The Potential Role of Dysfunctions in Neuron-Microglia Communication in the Pathogenesis of Brain Disorders

Chamera

Trojan

Szuster-Głuszczak

et al. 2020

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: The bidirectional communication between neurons and microglia is fundamental for the proper functioning of the central nervous system (CNS). Chemokines and clusters of differentiation (CD) along with their receptors represent ligand-receptor signalling that is uniquely important for neuron – microglia communication. Among these molecules, CX3CL1 (fractalkine) and CD200 (OX-2 membrane glycoprotein) come to the fore because of their cell-type-specific localization. They are principally expressed by neurons when their receptors, CX3CR1 and CD200R, respectively, are predominantly present on the microglia, resulting in the specific axis which maintains the CNS homeostasis. Disruptions to this balance are suggested as contributors or even the basis for many neurological diseases. : In this review, we discuss the roles of CX3CL1, CD200 and their receptors in both physiological and pathological processes within the CNS. We want to underline the critical involvement of these molecules in controlling neuron – microglia communication, noting that dysfunctions in their interactions constitute a key factor in severe neurological diseases, such as schizophrenia, depression and neurodegeneration-based conditions.

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“…As a demonstration of the important biological function performed by CXCL12, the amino acid sequence of this chemokine is extremely conserved among the different species during evolution. CXCL12 plays a role of primary importance already during embryonic development; experimental mouse models of gene knockout for CXCL12 or its CXCR4 receptor showed defects in the heart, intestines, circulatory and nervous systems, which are already lethal in the early stages of development ( 51 ). Furthermore, the lack of ability of the hematopoietic progenitors to colonize the bone marrow is significant, and this phenomenon can be related to the role of CXCL12 in regulating the migration of HSC and their trafficking between the different hematopoietic niches.…”

Section: Acute Lymphoblastic Leukemiamentioning

confidence: 99%

The Complexity of the Tumor Microenvironment and Its Role in Acute Lymphoblastic Leukemia: Implications for Therapies

et al. 2021

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The microenvironment that surrounds a tumor, in addition to the tumor itself, plays an important role in the onset of resistance to molecularly targeted therapies. Cancer cells and their microenvironment interact closely between them by means of a molecular communication that mutually influences their biological characteristics and behavior. Leukemia cells regulate the recruitment, activation and program of the cells of the surrounding microenvironment, including those of the immune system. Studies on the interactions between the bone marrow (BM) microenvironment and Acute Lymphoblastic Leukemia (ALL) cells have opened a scenario of potential therapeutic targets which include cytokines and their receptors, signal transduction networks, and hypoxia-related proteins. Hypoxia also enhances the formation of new blood vessels, and several studies show how angiogenesis could have a key role in the pathogenesis of ALL. Knowledge of the molecular mechanisms underlying tumor-microenvironment communication and angiogenesis could contribute to the early diagnosis of leukemia and to personalized molecular therapies. This article is part of a Special Issue entitled: Innovative Multi-Disciplinary Approaches for Precision Studies in Leukemia edited by Sandra Marmiroli (University of Modena and Reggio Emilia, Modena, Italy) and Xu Huang (University of Glasgow, Glasgow, United Kingdom).

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Knockdown of the CXCL12/CXCR7 chemokine pathway results in learning deficits and neural progenitor maturation impairment in mice

Cited by 10 publications

References 51 publications

Microglia induce the transformation of A1/A2 reactive astrocytes via the CXCR7/PI3K/Akt pathway in chronic post-surgical pain

Microglia induce the transformation of A1/A2 reactive astrocytes via the CXCR7/PI3K/Akt pathway in chronic post-surgical pain

The Potential Role of Dysfunctions in Neuron-Microglia Communication in the Pathogenesis of Brain Disorders

The Complexity of the Tumor Microenvironment and Its Role in Acute Lymphoblastic Leukemia: Implications for Therapies

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