Postnatal expression of CD38 in astrocytes regulates synapse formation and adult social memory
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE216887 | GEO | 2023/05/17
REPOSITORIES: GEO
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Project description:Postnatal expression of CD38 in astrocytes regulates synapse formation and adult social memory
| PRJNA896112 | ENA
Project description:Social behavior is essential for health, survival, and reproduction of animals; however, the role of astrocytes in social behavior remains largely unknown. The transmembrane protein CD38, which acts both as a receptor and ADP-ribosyl cyclase to produce cyclic ADP-ribose (cADPR) regulates social behaviors by promoting oxytocin release from hypothalamic neurons. CD38 is also abundantly expressed in astrocytes in the postnatal brain and is important for astroglial development. Here, we demonstrate that the astroglial-expressed CD38 plays an important role in social behavior during development. Selective deletion of CD38 in postnatal astrocytes, but not in adult astrocytes, impairs social memory without any other behavioral abnormalities. Morphological analysis shows that depletion of astroglial CD38 in the postnatal brain interferes with synapse formation in the medial prefrontal cortex (mPFC) and hippocampus. Moreover, astroglial CD38 expression promotes synaptogenesis of excitatory neurons by increasing the level of extracellular SPARCL1 (also known as Hevin), a synaptogenic protein. The release of SPARCL1 from astrocytes is regulated by CD38/cADPR/calcium signaling. These data demonstrate a novel developmental role of astrocytes in neural circuit formation and regulation of social behavior in adults.
| S-EPMC10390870 | biostudies-literature
Project description:Social behavior is essential for health, survival, and reproduction of animals; however, the role of astrocytes in social behavior remains largely unknown. The transmembrane protein CD38, which acts both as a receptor and ADP-ribosyl cyclase to produce cyclic ADP-ribose (cADPR) regulates social behaviors by promoting oxytocin release from hypothalamic neurons. CD38 is also abundantly expressed in astrocytes in the postnatal brain and is important for astroglial development. Here, we demonstrate that astroglial-expressed CD38 plays an important role in social behavior during development. Selective deletion of CD38 in postnatal astrocytes, but not in adult astrocytes, impairs social memory without any other behavioral abnormalities. Morphological analysis shows that depletion of astroglial CD38 in the postnatal brain interferes with synapse formation in the medial prefrontal cortex (mPFC) and hippocampus. Moreover, astroglial CD38 expression promotes synaptogenesis of excitatory neurons by increasing the level of extracellular SPARCL1 (also known as Hevin), a synaptogenic protein. The release of SPARCL1 from astrocytes is regulated by CD38/cADPR/calcium signaling. This data demonstrates a novel developmental role of astrocytes in neural circuit formation and regulation of social behavior in adults.
| S-SCDT-10_15252-EMBJ_2022111247 | biostudies-other
Project description:CD38 and CD49d are associated negative prognosticators in chronic lymphocytic leukemia (CLL). Despite evidence that both molecules are involved in interactions occurring between CLL and normal cells in the context of CLL-involved tissues, a functional link is still missing. Using gene expression profiles comparing CD38+CD49d+ vs. CD38-CD49d- CLL cells, we demonstrated overexpression of the CCL3 and CCL4 chemokines in cells from the former group. These chemokines were also upregulated by CD38 signals in CLL; moreover, CCL3 was expressed by CLL cells from bone marrow biopsies (BMB) of CD38+CD49d+ but not CD38-CD49d- cases. High levels of CCR1 and, to a lesser extent, CCR5, the receptors for CCL3 and CCL4, were found in CLL-derived monocyte-macrophages. Consistently, CCL3 increased monocyte migration, and CD68+ macrophage infiltration was particularly high in BMB from CD38+CD49d+ CLL. Conditioned media from CCL3-stimulated macrophages induced endothelial cells to express VCAM-1, the CD49d ligand, likely through TNFα over-production. These effects were apparent in BMB from CD38+CD49d+CLL, where lymphoid infiltrates were characterized by a prominent meshwork of VCAM-1+ stromal/endothelial cells. Lastly, CD49d engagement by VCAM-1-transfectants increased viability of CD38+CD49d+ CLL cells. Altogether, CD38 and CD49d can be thought of as a part of a consecutive chain of events ultimately leading to improved survival of CLL cells.
2009-03-03 | GSE14560 | GEO
Project description:Dysregulated neurite outgrowth and synapse formation underlie many psychiatric disorders. Wolfram syndrome (WS) mainly caused by WFS1 deficiency is a monogenic genetic disease manifested by severe psychiatric disorders. Due to athe lack of proper human disease models, the underlying mechanism is poorly understood. Particularly, whether and how WFS1 deficiency affects synapse formation remain elusive. By mirroring the complexity of human brain development with cerebral organoids derived from human embryonic stem cells (hESCs) harboring WFS1 loss of function (LOF), we found that WFS1-deficient cerebral organoids not only recapitulated the neuronal loss phenotype in WS patients, but also exhibited significantly impaired synapse formation associated with reduced astrocytes, suggesting a defective structural basis for psychiatric disorders elicited by WFS1 deficiency. To further unravel the complexity of interplay between neurons and astrocytes, each neural cell type was respectively differentiated from hESCs harboring WFS1 LOF. WFS1 deficiency in neurons autonomously delayed neuronal differentiation with altered expressions of genes associated with psychiatric disorders, and impaired neurite outgrowth and reduced synapse formation associated with elevated cytosolic calcium. Interestingly, WFS1 deficiency in astrocytes decreased the expression of glutamate transporter EAAT2 and compromised glutamate uptake, causing reduced neurite outgrowth with increased cytosolic calcium when co-cultured with wildtype (WT) neurons, highlighting pathogenic role of WFS1-deficient astrocytes. Importantly, restoring EAAT2 expression in astrocytes by riluzole treatment significantly alleviated reduced neurite outgrowth phenotype in WT neurons co-cultured with WFS1-deficient astrocytes. Altogether, our study provides novel insights into how WFS1 deficiency affects neurite outgrowth and synapse formation, potentially contributing to predisposition of psychiatric disorders, and offers a potential strategy of therapy.
2022-03-17 | GSE185052 | GEO
Project description:CD38 expression is an important prognostic marker in CLL with high levels of CD38 associated with shorter overall survival. In this study, we used gene expression profiling and protein analysis of highly purified cell-sorted CD38+ and CD38- chronic lymphocytic leukemia cells to elucidate a molecular basis for the association between CD38 expression and inferior clinical outcome. Paired CD38+ and CD38- CLL cells derived from the same patient were shown to be monoclonal by VH gene sequencing but despite this, CD38+ CLL cells possessed a distinct gene expression profile when compared with their CD38- sub-clones. Keywords: Sub-clonal analysis of CLL cells derived from the same leukemia sample
2006-11-23 | GSE6321 | GEO
Project description:To investigate the role of CD38 activity on astrocyte pro-inflmmatory activation
2022-08-12 | GSE205943 | GEO
Project description:Effect of depletion of CD38 on gene expression in LPS/IFNg-stimulated primary mouse astrocytes
| PRJNA848398 | ENA
Project description:Astroglial cells in the adult brain constitute a heterogeneous population endowed with region-specific properties. Recently, they have acquired greater relevance as active components of the adult neural stem cell (aNSC) niches. Astrocytes located in the vicinity of aNSC reservoirs are thought to regulate aNSC behaviour. We have compared the function of glial cells isolated from the postnatal and adult subventricular zone and hippocampus (two stem cell niches, where aNSCs self-renew and give rise to immature neurons), from the olfactory bulb (a neurogenic region where the immature neurons cease to proliferate and terminally differentiate) and from a non-stem and non-neurogenic area such as the ventral mesencephalon. Co-culture experiments demonstrate that subventricular zone glial cells secrete soluble signals that promote NSC self-renewing divisions. We used microarrays to detail the global gene expression of astroglial cells isolated from four different brain regions (olfactory bulb, ventral mesencephalon, hippocampus and subventricular zone) and identified up-regulated genes coding for secreted proteins in astrocytes from the subventricular zone. Primary astrocytes were cultured from four CD-1 mouse brain regions and cells were employed for RNA extraction and hybridization on Affymetrix microarrays. Primary tissue for the astrocyte cultures was dissected from four postnatal day 3 littermate pups. The tissue from the three pups was pooled in order to reduce individual differences of expression profiles.
2012-05-31 | E-GEOD-36456 | biostudies-arrayexpress
Project description:B-cell chronic lymphocytic leukemia (B-CLL) is a heterogenous disease with a highly variable clinical course and analysis of ZAP-70 and CD38 expression on B-CLL cells allowed for identification of patients with good (ZAP-70-CD38-), intermediate (discordant expression of ZAP-70 and CD38) and poor (ZAP-70+CD38+) prognosis. In an attempt to identify a molecular basis that may underly this diverse clinical behaviour DNA microarray technology was employed to compare eight ZAP-70+CD38+ with eight ZAP-70-CD38- B-CLL cases. We used microarrays to detail the global programme of gene expression distinguising B-CLL from patient with good (samples 1 to 8) and poor prognosis (sample 9 to 16) and identified distinct classes of up- and down-regulated genes. Keywords: Disease progression
2006-09-22 | GSE4392 | GEO